A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid
Identifieur interne : 000994 ( Pmc/Corpus ); précédent : 000993; suivant : 000995A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid
Auteurs : Sylvin Benjamin Ateba ; Marie Alfrede Mvondo ; Sefirin Djiogue ; Stéphane Zingué ; Liselotte Krenn ; Dieudonné NjamenSource :
- Frontiers in Pharmacology [ 1663-9812 ] ; 2019.
Abstract
Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective nonprenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological effects (therapeutic potential). In this review, we summarize the current information on health-promoting properties of AIF. Reported data evidenced that AIF has a multitherapeutic potential with antiosteoporotic, antioxidant and anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective properties. However, research on these aspects of AIF is not sufficient and needs to be reevaluated using more appropriate methods and methodology. Further series of studies are needed to confirm these pharmacological effects, and this review should lay the basis for the design of respective investigations. Overall, despite the drawbacks of studies recorded, AIF exhibits a potential as drug candidate.
Url:
DOI: 10.3389/fphar.2019.00952
PubMed: 31551770
PubMed Central: 6746831
Links to Exploration step
PMC:6746831Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid</title><author><name sortKey="Ateba, Sylvin Benjamin" sort="Ateba, Sylvin Benjamin" uniqKey="Ateba S" first="Sylvin Benjamin" last="Ateba">Sylvin Benjamin Ateba</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Mvondo, Marie Alfrede" sort="Mvondo, Marie Alfrede" uniqKey="Mvondo M" first="Marie Alfrede" last="Mvondo">Marie Alfrede Mvondo</name><affiliation><nlm:aff id="aff2"><institution>Research Unit of Animal Physiology and Phytopharmacology, Department of Animal Biology, Faculty of Science, University of Dschang</institution>,<addr-line>Dschang</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Djiogue, Sefirin" sort="Djiogue, Sefirin" uniqKey="Djiogue S" first="Sefirin" last="Djiogue">Sefirin Djiogue</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Zingue, Stephane" sort="Zingue, Stephane" uniqKey="Zingue S" first="Stéphane" last="Zingué">Stéphane Zingué</name><affiliation><nlm:aff id="aff3"><institution>Department of Life and Earth Sciences, Higher Teachers’ Training College, University of Maroua</institution>,<addr-line>Maroua</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Krenn, Liselotte" sort="Krenn, Liselotte" uniqKey="Krenn L" first="Liselotte" last="Krenn">Liselotte Krenn</name><affiliation><nlm:aff id="aff4"><institution>Department of Pharmacognosy, University of Vienna, Vienna</institution>,<country>Austria</country></nlm:aff></affiliation></author><author><name sortKey="Njamen, Dieudonne" sort="Njamen, Dieudonne" uniqKey="Njamen D" first="Dieudonné" last="Njamen">Dieudonné Njamen</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31551770</idno><idno type="pmc">6746831</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746831</idno><idno type="RBID">PMC:6746831</idno><idno type="doi">10.3389/fphar.2019.00952</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000994</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000994</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid</title><author><name sortKey="Ateba, Sylvin Benjamin" sort="Ateba, Sylvin Benjamin" uniqKey="Ateba S" first="Sylvin Benjamin" last="Ateba">Sylvin Benjamin Ateba</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Mvondo, Marie Alfrede" sort="Mvondo, Marie Alfrede" uniqKey="Mvondo M" first="Marie Alfrede" last="Mvondo">Marie Alfrede Mvondo</name><affiliation><nlm:aff id="aff2"><institution>Research Unit of Animal Physiology and Phytopharmacology, Department of Animal Biology, Faculty of Science, University of Dschang</institution>,<addr-line>Dschang</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Djiogue, Sefirin" sort="Djiogue, Sefirin" uniqKey="Djiogue S" first="Sefirin" last="Djiogue">Sefirin Djiogue</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Zingue, Stephane" sort="Zingue, Stephane" uniqKey="Zingue S" first="Stéphane" last="Zingué">Stéphane Zingué</name><affiliation><nlm:aff id="aff3"><institution>Department of Life and Earth Sciences, Higher Teachers’ Training College, University of Maroua</institution>,<addr-line>Maroua</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author><author><name sortKey="Krenn, Liselotte" sort="Krenn, Liselotte" uniqKey="Krenn L" first="Liselotte" last="Krenn">Liselotte Krenn</name><affiliation><nlm:aff id="aff4"><institution>Department of Pharmacognosy, University of Vienna, Vienna</institution>,<country>Austria</country></nlm:aff></affiliation></author><author><name sortKey="Njamen, Dieudonne" sort="Njamen, Dieudonne" uniqKey="Njamen D" first="Dieudonné" last="Njamen">Dieudonné Njamen</name><affiliation><nlm:aff id="aff1"><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></nlm:aff></affiliation></author></analytic><series><title level="j">Frontiers in Pharmacology</title><idno type="eISSN">1663-9812</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective nonprenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological effects (therapeutic potential). In this review, we summarize the current information on health-promoting properties of AIF. Reported data evidenced that AIF has a multitherapeutic potential with antiosteoporotic, antioxidant and anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective properties. However, research on these aspects of AIF is not sufficient and needs to be reevaluated using more appropriate methods and methodology. Further series of studies are needed to confirm these pharmacological effects, and this review should lay the basis for the design of respective investigations. Overall, despite the drawbacks of studies recorded, AIF exhibits a potential as drug candidate.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akter, K" uniqKey="Akter K">K. Akter</name></author><author><name sortKey="Barnes, E C" uniqKey="Barnes E">E. C. Barnes</name></author><author><name sortKey="Loa Kum Cheung, W L" uniqKey="Loa Kum Cheung W">W. L. Loa-Kum-Cheung</name></author><author><name sortKey="Yin, P" uniqKey="Yin P">P. Yin</name></author><author><name sortKey="Kichu, M" uniqKey="Kichu M">M. Kichu</name></author><author><name sortKey="Brophy, J J" uniqKey="Brophy J">J. J. Brophy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Altaf, M" uniqKey="Altaf M">M. Altaf</name></author><author><name sortKey="Miller, C H" uniqKey="Miller C">C. H. Miller</name></author><author><name sortKey="Bellows, D S" uniqKey="Bellows D">D. S. Bellows</name></author><author><name sortKey="O Oole, R" uniqKey="O Oole R">R. O’Toole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amen, Y M" uniqKey="Amen Y">Y. M. Amen</name></author><author><name sortKey="Marzouk, A M" uniqKey="Marzouk A">A. M. Marzouk</name></author><author><name sortKey="Zaghloul, M G" uniqKey="Zaghloul M">M. G. Zaghloul</name></author><author><name sortKey="Afifi, M S" uniqKey="Afifi M">M. S. Afifi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ateba, S B" uniqKey="Ateba S">S. B. Ateba</name></author><author><name sortKey="Mvondo, M A" uniqKey="Mvondo M">M. A. Mvondo</name></author><author><name sortKey="Tchoukouegno Ngueu, S" uniqKey="Tchoukouegno Ngueu S">S. Tchoukouegno Ngueu</name></author><author><name sortKey="Tchoumtchoua, J" uniqKey="Tchoumtchoua J">J. Tchoumtchoua</name></author><author><name sortKey="Awounfack, C" uniqKey="Awounfack C">C. Awounfack</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ayine Tora, D M" uniqKey="Ayine Tora D">D. M. Ayine-Tora</name></author><author><name sortKey="Kingsford Adaboh, R" uniqKey="Kingsford Adaboh R">R. Kingsford-Adaboh</name></author><author><name sortKey="Asomaning, W A" uniqKey="Asomaning W">W. A. Asomaning</name></author><author><name sortKey="Harrison, J J E K" uniqKey="Harrison J">J. J. E. K. Harrison</name></author><author><name sortKey="Mills Robertson, F C" uniqKey="Mills Robertson F">F. C. Mills-Robertson</name></author><author><name sortKey="Bukari, Y" uniqKey="Bukari Y">Y. Bukari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Balouiri, M" uniqKey="Balouiri M">M. Balouiri</name></author><author><name sortKey="Sadiki, M" uniqKey="Sadiki M">M. Sadiki</name></author><author><name sortKey="Ibnsouda, S K" uniqKey="Ibnsouda S">S. K. Ibnsouda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ben David, U" uniqKey="Ben David U">U. Ben-David</name></author><author><name sortKey="Ha, G" uniqKey="Ha G">G. Ha</name></author><author><name sortKey="Tseng, Y Y" uniqKey="Tseng Y">Y.-Y. Tseng</name></author><author><name sortKey="Greenwald, N F" uniqKey="Greenwald N">N. F. Greenwald</name></author><author><name sortKey="Oh, C" uniqKey="Oh C">C. Oh</name></author><author><name sortKey="Shih, J" uniqKey="Shih J">J. Shih</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benzie, I F F" uniqKey="Benzie I">I. F. F. Benzie</name></author><author><name sortKey="Strain, J J" uniqKey="Strain J">J. J. Strain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bernini, R" uniqKey="Bernini R">R. Bernini</name></author><author><name sortKey="Crisante, F" uniqKey="Crisante F">F. Crisante</name></author><author><name sortKey="Ginnasi, M C" uniqKey="Ginnasi M">M. C. Ginnasi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boik, J" uniqKey="Boik J">J. Boik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="B Rquez, J" uniqKey="B Rquez J">J. Bórquez</name></author><author><name sortKey="Kennelly, E J" uniqKey="Kennelly E">E. J. Kennelly</name></author><author><name sortKey="Simirgiotis, M J" uniqKey="Simirgiotis M">M. J. Simirgiotis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Botta, B" uniqKey="Botta B">B. Botta</name></author><author><name sortKey="Menendez, P" uniqKey="Menendez P">P. Menendez</name></author><author><name sortKey="Zappia, G" uniqKey="Zappia G">G. Zappia</name></author><author><name sortKey="De Lima, R A" uniqKey="De Lima R">R. A. de Lima</name></author><author><name sortKey="Torge, R" uniqKey="Torge R">R. Torge</name></author><author><name sortKey="Monache, G D" uniqKey="Monache G">G. D. Monache</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Botta, B" uniqKey="Botta B">B. Botta</name></author><author><name sortKey="Vitali, A" uniqKey="Vitali A">A. Vitali</name></author><author><name sortKey="Menendez, P" uniqKey="Menendez P">P. Menendez</name></author><author><name sortKey="Misiti, D" uniqKey="Misiti D">D. Misiti</name></author><author><name sortKey="Monache, G D" uniqKey="Monache G">G. D. Monache</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaturvedi, V" uniqKey="Chaturvedi V">V. Chaturvedi</name></author><author><name sortKey="Dwivedi, N" uniqKey="Dwivedi N">N. Dwivedi</name></author><author><name sortKey="Tripathi, R P" uniqKey="Tripathi R">R. P. Tripathi</name></author><author><name sortKey="Sinha, S" uniqKey="Sinha S">S. Sinha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaudhury, A" uniqKey="Chaudhury A">A. Chaudhury</name></author><author><name sortKey="Duvoor, C" uniqKey="Duvoor C">C. Duvoor</name></author><author><name sortKey="Reddy Dendi, V S" uniqKey="Reddy Dendi V">V. S. Reddy Dendi</name></author><author><name sortKey="Kraleti, S" uniqKey="Kraleti S">S. Kraleti</name></author><author><name sortKey="Chada, A" uniqKey="Chada A">A. Chada</name></author><author><name sortKey="Ravilla, R" uniqKey="Ravilla R">R. Ravilla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, L W" uniqKey="Chen L">L. W. Chen</name></author><author><name sortKey="Cheng, M J" uniqKey="Cheng M">M. J. Cheng</name></author><author><name sortKey="Peng, C F" uniqKey="Peng C">C. F. Peng</name></author><author><name sortKey="Chen, I S" uniqKey="Chen I">I. S. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X. Chen</name></author><author><name sortKey="Mukwaya, E" uniqKey="Mukwaya E">E. Mukwaya</name></author><author><name sortKey="Wong, M S" uniqKey="Wong M">M. S. Wong</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chukwujekwu, J C" uniqKey="Chukwujekwu J">J. C. Chukwujekwu</name></author><author><name sortKey="Van Heerden, F R" uniqKey="Van Heerden F">F. R. Van Heerden</name></author><author><name sortKey="Van Staden, J" uniqKey="Van Staden J">J. Van Staden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey=", M" uniqKey=" M">M. Číž</name></author><author><name sortKey=" Ova, H" uniqKey=" Ova H">H. Čížová</name></author><author><name sortKey="Denev, P" uniqKey="Denev P">P. Denev</name></author><author><name sortKey="Kratchanova, M" uniqKey="Kratchanova M">M. Kratchanova</name></author><author><name sortKey="Slavov, A" uniqKey="Slavov A">A. Slavov</name></author><author><name sortKey="Lojek, A" uniqKey="Lojek A">A. Lojek</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cong, W" uniqKey="Cong W">W. Cong</name></author><author><name sortKey="Zhou, C" uniqKey="Zhou C">C. Zhou</name></author><author><name sortKey="Yin, J" uniqKey="Yin J">J. Yin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cos, P" uniqKey="Cos P">P. Cos</name></author><author><name sortKey="Vlietinck, A J" uniqKey="Vlietinck A">A. J. Vlietinck</name></author><author><name sortKey="Berghe, D V" uniqKey="Berghe D">D. V. Berghe</name></author><author><name sortKey="Maes, L" uniqKey="Maes L">L. Maes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dai, J" uniqKey="Dai J">J. Dai</name></author><author><name sortKey="Shen, D" uniqKey="Shen D">D. Shen</name></author><author><name sortKey="Yoshida, W Y" uniqKey="Yoshida W">W. Y. Yoshida</name></author><author><name sortKey="Parrish, S M" uniqKey="Parrish S">S. M. Parrish</name></author><author><name sortKey="Williams, P G" uniqKey="Williams P">P. G. Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dandekar, A" uniqKey="Dandekar A">A. Dandekar</name></author><author><name sortKey="Mendez, R" uniqKey="Mendez R">R. Mendez</name></author><author><name sortKey="Zhang, K" uniqKey="Zhang K">K. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dendup, T" uniqKey="Dendup T">T. Dendup</name></author><author><name sortKey="Prachyawarakorn, V" uniqKey="Prachyawarakorn V">V. Prachyawarakorn</name></author><author><name sortKey="Pansanit, A" uniqKey="Pansanit A">A. Pansanit</name></author><author><name sortKey="Mahidol, C" uniqKey="Mahidol C">C. Mahidol</name></author><author><name sortKey="Ruchirawat, S" uniqKey="Ruchirawat S">S. Ruchirawat</name></author><author><name sortKey="Kittakoop, P" uniqKey="Kittakoop P">P. Kittakoop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Djiogue, S" uniqKey="Djiogue S">S. Djiogue</name></author><author><name sortKey="Halabalaki, M" uniqKey="Halabalaki M">M. Halabalaki</name></author><author><name sortKey="Alexi, X" uniqKey="Alexi X">X. Alexi</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Fomum, Z T" uniqKey="Fomum Z">Z. T. Fomum</name></author><author><name sortKey="Alexis, M N" uniqKey="Alexis M">M. N. Alexis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Djiogue, S" uniqKey="Djiogue S">S. Djiogue</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Halabalaki, M" uniqKey="Halabalaki M">M. Halabalaki</name></author><author><name sortKey="Kretzschmar, G" uniqKey="Kretzschmar G">G. Kretzschmar</name></author><author><name sortKey="Beyer, A" uniqKey="Beyer A">A. Beyer</name></author><author><name sortKey="Mbanya, J C" uniqKey="Mbanya J">J. C. Mbanya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Egermann, M" uniqKey="Egermann M">M. Egermann</name></author><author><name sortKey="Goldhahn, J" uniqKey="Goldhahn J">J. Goldhahn</name></author><author><name sortKey="Schneider, E" uniqKey="Schneider E">E. Schneider</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Edziri, H" uniqKey="Edziri H">H. Edziri</name></author><author><name sortKey="Mastouri, M" uniqKey="Mastouri M">M. Mastouri</name></author><author><name sortKey="Mahjoub, M A" uniqKey="Mahjoub M">M. A. Mahjoub</name></author><author><name sortKey="Mighri, Z" uniqKey="Mighri Z">Z. Mighri</name></author><author><name sortKey="Mahjoub, A" uniqKey="Mahjoub A">A. Mahjoub</name></author><author><name sortKey="Verschaeve, L" uniqKey="Verschaeve L">L. Verschaeve</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Floegel, A" uniqKey="Floegel A">A. Floegel</name></author><author><name sortKey="Kim, D O" uniqKey="Kim D">D. O. Kim</name></author><author><name sortKey="Chung, S J" uniqKey="Chung S">S. J. Chung</name></author><author><name sortKey="Koo, S I" uniqKey="Koo S">S. I. Koo</name></author><author><name sortKey="Chun, O K" uniqKey="Chun O">O. K. Chun</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fu, G" uniqKey="Fu G">G. Fu</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author><author><name sortKey="Huang, X" uniqKey="Huang X">X. Huang</name></author><author><name sortKey="Zhang, R" uniqKey="Zhang R">R. Zhang</name></author><author><name sortKey="Tian, K" uniqKey="Tian K">K. Tian</name></author><author><name sortKey="Hou, S" uniqKey="Hou S">S. Hou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gao, M" uniqKey="Gao M">M. Gao</name></author><author><name sortKey="Chang, Y" uniqKey="Chang Y">Y. Chang</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Ban, C" uniqKey="Ban C">C. Ban</name></author><author><name sortKey="Zhang, F" uniqKey="Zhang F">F. Zhang</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Han, X H" uniqKey="Han X">X. H. Han</name></author><author><name sortKey="Hong, S S" uniqKey="Hong S">S. S. Hong</name></author><author><name sortKey="Hwang, J S" uniqKey="Hwang J">J. S. Hwang</name></author><author><name sortKey="Jeong, S H" uniqKey="Jeong S">S. H. Jeong</name></author><author><name sortKey="Hwang, J H" uniqKey="Hwang J">J. H. Hwang</name></author><author><name sortKey="Lee, M H" uniqKey="Lee M">M. H. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, Y" uniqKey="Han Y">Y. Han</name></author><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Zhao, N" uniqKey="Zhao N">N. Zhao</name></author><author><name sortKey="Peng, J" uniqKey="Peng J">J. Peng</name></author><author><name sortKey="Gao, H" uniqKey="Gao H">H. Gao</name></author><author><name sortKey="Qiu, X" uniqKey="Qiu X">X. Qiu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Heikkila, R E" uniqKey="Heikkila R">R. E. Heikkila</name></author><author><name sortKey="Sonsalla, P K" uniqKey="Sonsalla P">P. K. Sonsalla</name></author><author><name sortKey="Duvoisin, R C" uniqKey="Duvoisin R">R. C. Duvoisin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hendrickx, G" uniqKey="Hendrickx G">G. Hendrickx</name></author><author><name sortKey="Boudin, E" uniqKey="Boudin E">E. Boudin</name></author><author><name sortKey="Van Hul, W" uniqKey="Van Hul W">W. Van Hul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hiep, N T" uniqKey="Hiep N">N. T. Hiep</name></author><author><name sortKey="Kwon, J" uniqKey="Kwon J">J. Kwon</name></author><author><name sortKey="Kim, D W" uniqKey="Kim D">D.-W. Kim</name></author><author><name sortKey="Hwang, B Y" uniqKey="Hwang B">B. Y. Hwang</name></author><author><name sortKey="Lee, H J" uniqKey="Lee H">H.-J. Lee</name></author><author><name sortKey="Mar, W" uniqKey="Mar W">W. Mar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hiep, N T" uniqKey="Hiep N">N. T. Hiep</name></author><author><name sortKey="Kwon, J" uniqKey="Kwon J">J. Kwon</name></author><author><name sortKey="Kim, D W" uniqKey="Kim D">D.-W. Kim</name></author><author><name sortKey="Hong, S" uniqKey="Hong S">S. Hong</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y. Guo</name></author><author><name sortKey="Hwang, B Y" uniqKey="Hwang B">B. Y. Hwang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, S" uniqKey="Hong S">S. Hong</name></author><author><name sortKey="Kwon, J" uniqKey="Kwon J">J. Kwon</name></author><author><name sortKey="Hiep, N T" uniqKey="Hiep N">N. T. Hiep</name></author><author><name sortKey="Sim, S J" uniqKey="Sim S">S. J. Sim</name></author><author><name sortKey="Kim, N" uniqKey="Kim N">N. Kim</name></author><author><name sortKey="Kim, K H" uniqKey="Kim K">K. H. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y. Hu</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Wang, L" uniqKey="Wang L">L. Wang</name></author><author><name sortKey="Deng, L" uniqKey="Deng L">L. Deng</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J. Sun</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X. Jiang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, D" uniqKey="Huang D">D. Huang</name></author><author><name sortKey="Ou, B" uniqKey="Ou B">B. Ou</name></author><author><name sortKey="Prior, R L" uniqKey="Prior R">R. L. Prior</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, C" uniqKey="Ito C">C. Ito</name></author><author><name sortKey="Itoigawa, M" uniqKey="Itoigawa M">M. Itoigawa</name></author><author><name sortKey="Tan, H T W" uniqKey="Tan H">H. T. W. Tan</name></author><author><name sortKey="Tokuda, H" uniqKey="Tokuda H">H. Tokuda</name></author><author><name sortKey="Mou, X Y" uniqKey="Mou X">X. Y. Mou</name></author><author><name sortKey="Mukainaka, T" uniqKey="Mukainaka T">T. Mukainaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jackson, B" uniqKey="Jackson B">B. Jackson</name></author><author><name sortKey="Owen, P J" uniqKey="Owen P">P. J. Owen</name></author><author><name sortKey="Scheinmann, F" uniqKey="Scheinmann F">F. Scheinmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jorgensen, J H" uniqKey="Jorgensen J">J. H. Jorgensen</name></author><author><name sortKey="Ferraro, M J" uniqKey="Ferraro M">M. J. Ferraro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kenny, C R" uniqKey="Kenny C">C. R. Kenny</name></author><author><name sortKey="Furey, A" uniqKey="Furey A">A. Furey</name></author><author><name sortKey="Lucey, B" uniqKey="Lucey B">B. Lucey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalid, S A" uniqKey="Khalid S">S. A. Khalid</name></author><author><name sortKey="Farouk, A" uniqKey="Farouk A">A. Farouk</name></author><author><name sortKey="Geary, T G" uniqKey="Geary T">T. G. Geary</name></author><author><name sortKey="Jensen, J B" uniqKey="Jensen J">J. B. Jensen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, D W" uniqKey="Kim D">D. W. Kim</name></author><author><name sortKey="Kwon, J" uniqKey="Kwon J">J. Kwon</name></author><author><name sortKey="Sim, S J" uniqKey="Sim S">S. J. Sim</name></author><author><name sortKey="Lee, D" uniqKey="Lee D">D. Lee</name></author><author><name sortKey="Mar, W" uniqKey="Mar W">W. Mar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuete, V" uniqKey="Kuete V">V. Kuete</name></author><author><name sortKey="Mbaveng, A T" uniqKey="Mbaveng A">A. T. Mbaveng</name></author><author><name sortKey="Nono, E C N" uniqKey="Nono E">E. C. N. Nono</name></author><author><name sortKey="Simo, C C" uniqKey="Simo C">C. C. Simo</name></author><author><name sortKey="Zeino, M" uniqKey="Zeino M">M. Zeino</name></author><author><name sortKey="Nkengfack, A E" uniqKey="Nkengfack A">A. E. Nkengfack</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuete, V" uniqKey="Kuete V">V. Kuete</name></author><author><name sortKey="Ngameni, B" uniqKey="Ngameni B">B. Ngameni</name></author><author><name sortKey="Fotso Simo, C C" uniqKey="Fotso Simo C">C. C. Fotso Simo</name></author><author><name sortKey="Kengap Tankeu, R" uniqKey="Kengap Tankeu R">R. Kengap Tankeu</name></author><author><name sortKey="Tchaleu Ngadjui, B" uniqKey="Tchaleu Ngadjui B">B. Tchaleu Ngadjui</name></author><author><name sortKey="Meyer, J J M" uniqKey="Meyer J">J. J. M. Meyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, S" uniqKey="Kumar S">S. Kumar</name></author><author><name sortKey="Pandey, A K" uniqKey="Pandey A">A. K. Pandey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, S" uniqKey="Kumar S">S. Kumar</name></author><author><name sortKey="Pathania, A S" uniqKey="Pathania A">A. S. Pathania</name></author><author><name sortKey="Saxena, A K" uniqKey="Saxena A">A. K. Saxena</name></author><author><name sortKey="Vishwakarma, R A" uniqKey="Vishwakarma R">R. A. Vishwakarma</name></author><author><name sortKey="Ali, A" uniqKey="Ali A">A. Ali</name></author><author><name sortKey="Bhushan, S" uniqKey="Bhushan S">S. Bhushan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, M N T" uniqKey="Lambert M">M. N. T. Lambert</name></author><author><name sortKey="Jeppesen, P B" uniqKey="Jeppesen P">P. B. Jeppesen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Landgraf, M" uniqKey="Landgraf M">M. Landgraf</name></author><author><name sortKey="Mcgovern, J A" uniqKey="Mcgovern J">J. A. McGovern</name></author><author><name sortKey="Fried, P" uniqKey="Fried P">P. Fried</name></author><author><name sortKey="Hutmacher, D W" uniqKey="Hutmacher D">D. W. Hutmacher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lap K, O" uniqKey="Lap K O">O. Lapčík</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, J S" uniqKey="Lee J">J. S. Lee</name></author><author><name sortKey="Oh, W K" uniqKey="Oh W">W. K. Oh</name></author><author><name sortKey="Ahn, J S" uniqKey="Ahn J">J. S. Ahn</name></author><author><name sortKey="Kim, Y H" uniqKey="Kim Y">Y. H. Kim</name></author><author><name sortKey="Mbafor, J T" uniqKey="Mbafor J">J. T. Mbafor</name></author><author><name sortKey="Wandji, J" uniqKey="Wandji J">J. Wandji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, M S" uniqKey="Lee M">M. S. Lee</name></author><author><name sortKey="Kim, C H" uniqKey="Kim C">C. H. Kim</name></author><author><name sortKey="Hoang, D M" uniqKey="Hoang D">D. M. Hoang</name></author><author><name sortKey="Kim, B Y" uniqKey="Kim B">B. Y. Kim</name></author><author><name sortKey="Sohn, C B" uniqKey="Sohn C">C. B. Sohn</name></author><author><name sortKey="Kim, M R" uniqKey="Kim M">M. R. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Legler, J" uniqKey="Legler J">J. Legler</name></author><author><name sortKey="Van Den Brink, C E" uniqKey="Van Den Brink C">C. E. van den Brink</name></author><author><name sortKey="Brouwer, A" uniqKey="Brouwer A">A. Brouwer</name></author><author><name sortKey="Murk, A J" uniqKey="Murk A">A. J. Murk</name></author><author><name sortKey="Van Der Saag, P T" uniqKey="Van Der Saag P">P. T. van der Saag</name></author><author><name sortKey="Vethaak, A D" uniqKey="Vethaak A">A. D. Vethaak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lelovas, P P" uniqKey="Lelovas P">P. P. Lelovas</name></author><author><name sortKey="Xanthos, T T" uniqKey="Xanthos T">T. T. Xanthos</name></author><author><name sortKey="Thoma, S E" uniqKey="Thoma S">S. E. Thoma</name></author><author><name sortKey="Lyritis, G P" uniqKey="Lyritis G">G. P. Lyritis</name></author><author><name sortKey="Dontas, I A" uniqKey="Dontas I">I. A. Dontas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leusch, F L" uniqKey="Leusch F">F. L. Leusch</name></author><author><name sortKey="De Jager, C" uniqKey="De Jager C">C. De Jager</name></author><author><name sortKey="Levi, Y" uniqKey="Levi Y">Y. Levi</name></author><author><name sortKey="Lim, R" uniqKey="Lim R">R. Lim</name></author><author><name sortKey="Puijker, L" uniqKey="Puijker L">L. Puijker</name></author><author><name sortKey="Sacher, F" uniqKey="Sacher F">F. Sacher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, D" uniqKey="Li D">D. Li</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Li, G" uniqKey="Li G">G. Li</name></author><author><name sortKey="Meng, Y" uniqKey="Meng Y">Y. Meng</name></author><author><name sortKey="Jin, Y" uniqKey="Jin Y">Y. Jin</name></author><author><name sortKey="Shang, S" uniqKey="Shang S">S. Shang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, P Y" uniqKey="Li P">P. Y. Li</name></author><author><name sortKey="Liang, Y C" uniqKey="Liang Y">Y. C. Liang</name></author><author><name sortKey="Sheu, M J" uniqKey="Sheu M">M. J. Sheu</name></author><author><name sortKey="Huang, S S" uniqKey="Huang S">S. S. Huang</name></author><author><name sortKey="Chao, C Y" uniqKey="Chao C">C. Y. Chao</name></author><author><name sortKey="Kuo, Y H" uniqKey="Kuo Y">Y. H. Kuo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, K" uniqKey="Li K">K. Li</name></author><author><name sortKey="Ji, S" uniqKey="Ji S">S. Ji</name></author><author><name sortKey="Song, W" uniqKey="Song W">W. Song</name></author><author><name sortKey="Kuang, Y" uniqKey="Kuang Y">Y. Kuang</name></author><author><name sortKey="Lin, Y" uniqKey="Lin Y">Y. Lin</name></author><author><name sortKey="Tang, S" uniqKey="Tang S">S. Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, X C" uniqKey="Li X">X. C. Li</name></author><author><name sortKey="Joshi, A S" uniqKey="Joshi A">A. S. Joshi</name></author><author><name sortKey="Elsohly, H N" uniqKey="Elsohly H">H. N. ElSohly</name></author><author><name sortKey="Khan, S I" uniqKey="Khan S">S. I. Khan</name></author><author><name sortKey="Jacob, M R" uniqKey="Jacob M">M. R. Jacob</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lim, J Y" uniqKey="Lim J">J. Y. Lim</name></author><author><name sortKey="Hwang, B Y" uniqKey="Hwang B">B. Y. Hwang</name></author><author><name sortKey="Hwang, K W" uniqKey="Hwang K">K. W. Hwang</name></author><author><name sortKey="Park, S Y" uniqKey="Park S">S. Y. Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Veena, C K" uniqKey="Veena C">C. K. Veena</name></author><author><name sortKey="Brian Morgan, J" uniqKey="Brian Morgan J">J. Brian Morgan</name></author><author><name sortKey="Mohammed, K A" uniqKey="Mohammed K">K. A. Mohammed</name></author><author><name sortKey="Jekabsons, M B" uniqKey="Jekabsons M">M. B. Jekabsons</name></author><author><name sortKey="Nagle, D G" uniqKey="Nagle D">D. G. Nagle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lyddiard, J R A" uniqKey="Lyddiard J">J. R. A. Lyddiard</name></author><author><name sortKey="Whitfield, P J" uniqKey="Whitfield P">P. J. Whitfield</name></author><author><name sortKey="Bartl, A" uniqKey="Bartl A">A. Bartl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ma, D F" uniqKey="Ma D">D. F. Ma</name></author><author><name sortKey="Qin, L Q" uniqKey="Qin L">L. Q. Qin</name></author><author><name sortKey="Wang, P Y" uniqKey="Wang P">P. Y. Wang</name></author><author><name sortKey="Katoh, R" uniqKey="Katoh R">R. Katoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magne Nde, C B" uniqKey="Magne Nde C">C. B. Magne Nde</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Fomum, S T" uniqKey="Fomum S">S. T. Fomum</name></author><author><name sortKey="Wandji, J" uniqKey="Wandji J">J. Wandji</name></author><author><name sortKey="Simpson, E" uniqKey="Simpson E">E. Simpson</name></author><author><name sortKey="Clyne, C" uniqKey="Clyne C">C. Clyne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magne Nde, C B" uniqKey="Magne Nde C">C. B. Magne Nde</name></author><author><name sortKey="Zingue, S" uniqKey="Zingue S">S. Zingue</name></author><author><name sortKey="Winter, E" uniqKey="Winter E">E. Winter</name></author><author><name sortKey="Creczynski Pasa, T B" uniqKey="Creczynski Pasa T">T. B. Creczynski-Pasa</name></author><author><name sortKey="Michel, T" uniqKey="Michel T">T. Michel</name></author><author><name sortKey="Fernandez, X" uniqKey="Fernandez X">X. Fernandez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Markovski, A" uniqKey="Markovski A">A. Markovski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Massoud, G N" uniqKey="Massoud G">G. N. Massoud</name></author><author><name sortKey="Li, W" uniqKey="Li W">W. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Matsuda, H" uniqKey="Matsuda H">H. Matsuda</name></author><author><name sortKey="Yoshida, K" uniqKey="Yoshida K">K. Yoshida</name></author><author><name sortKey="Miyagawa, K" uniqKey="Miyagawa K">K. Miyagawa</name></author><author><name sortKey="Asao, Y" uniqKey="Asao Y">Y. Asao</name></author><author><name sortKey="Takayama, S" uniqKey="Takayama S">S. Takayama</name></author><author><name sortKey="Nakashima, S" uniqKey="Nakashima S">S. Nakashima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mishra, K" uniqKey="Mishra K">K. Mishra</name></author><author><name sortKey="Ojha, H" uniqKey="Ojha H">H. Ojha</name></author><author><name sortKey="Chaudhury, N K" uniqKey="Chaudhury N">N. K. Chaudhury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mukai, R" uniqKey="Mukai R">R. Mukai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mvondo, M A" uniqKey="Mvondo M">M. A. Mvondo</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Tanee Fomum, S" uniqKey="Tanee Fomum S">S. Tanee Fomum</name></author><author><name sortKey="Wandji, J" uniqKey="Wandji J">J. Wandji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mvondo, M A" uniqKey="Mvondo M">M. A. Mvondo</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Fomum, S T" uniqKey="Fomum S">S. T. Fomum</name></author><author><name sortKey="Wandji, J" uniqKey="Wandji J">J. Wandji</name></author><author><name sortKey="Vollmer, G" uniqKey="Vollmer G">G. Vollmer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mvondo, M A" uniqKey="Mvondo M">M. A. Mvondo</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Kretzschmar, G" uniqKey="Kretzschmar G">G. Kretzschmar</name></author><author><name sortKey="Bader, M I" uniqKey="Bader M">M. I. Bader</name></author><author><name sortKey="Fomum, S T" uniqKey="Fomum S">S. T. Fomum</name></author><author><name sortKey="Wandji, J" uniqKey="Wandji J">J. Wandji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Na, M K" uniqKey="Na M">M. K. Na</name></author><author><name sortKey="Jang, J P" uniqKey="Jang J">J. P. Jang</name></author><author><name sortKey="Njamen, D" uniqKey="Njamen D">D. Njamen</name></author><author><name sortKey="Mbafor, J T" uniqKey="Mbafor J">J. T. Mbafor</name></author><author><name sortKey="Fomum, Z T" uniqKey="Fomum Z">Z. T. Fomum</name></author><author><name sortKey="Kim, B Y" uniqKey="Kim B">B. Y. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Namkoong, S" uniqKey="Namkoong S">S. Namkoong</name></author><author><name sortKey="Kim, T J" uniqKey="Kim T">T. J. Kim</name></author><author><name sortKey="Jang, I S" uniqKey="Jang I">I. S. Jang</name></author><author><name sortKey="Kang, K W" uniqKey="Kang K">K. W. Kang</name></author><author><name sortKey="Oh, W K" uniqKey="Oh W">W. K. Oh</name></author><author><name sortKey="Park, J" uniqKey="Park J">J. Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Namouchi, A" uniqKey="Namouchi A">A. Namouchi</name></author><author><name sortKey="Cimino, M" uniqKey="Cimino M">M. Cimino</name></author><author><name sortKey="Favre Rochex, S" uniqKey="Favre Rochex S">S. Favre-Rochex</name></author><author><name sortKey="Charles, P" uniqKey="Charles P">P. Charles</name></author><author><name sortKey="Gicquel, B" uniqKey="Gicquel B">B. Gicquel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nana, F" uniqKey="Nana F">F. Nana</name></author><author><name sortKey="Sandjo, L S" uniqKey="Sandjo L">L. S. Sandjo</name></author><author><name sortKey="Keumedjio, F" uniqKey="Keumedjio F">F. Keumedjio</name></author><author><name sortKey="Ambassa, P" uniqKey="Ambassa P">P. Ambassa</name></author><author><name sortKey="Malik, R" uniqKey="Malik R">R. Malik</name></author><author><name sortKey="Kuete, V" uniqKey="Kuete V">V. Kuete</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Naoi, M" uniqKey="Naoi M">M. Naoi</name></author><author><name sortKey="Maruyama, W" uniqKey="Maruyama W">W. Maruyama</name></author><author><name sortKey="Shamoto Nagai, M" uniqKey="Shamoto Nagai M">M. Shamoto-Nagai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ncube, N S" uniqKey="Ncube N">N. S. Ncube</name></author><author><name sortKey="Afolayan, A J" uniqKey="Afolayan A">A. J. Afolayan</name></author><author><name sortKey="Okoh, A I" uniqKey="Okoh A">A. I. Okoh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ndemangou, B" uniqKey="Ndemangou B">B. Ndemangou</name></author><author><name sortKey="Tedjon Sielinou, V" uniqKey="Tedjon Sielinou V">V. Tedjon Sielinou</name></author><author><name sortKey="Vardamides, J C" uniqKey="Vardamides J">J. C. Vardamides</name></author><author><name sortKey="Shaiq Ali, M" uniqKey="Shaiq Ali M">M. Shaiq Ali</name></author><author><name sortKey="Lateef, M" uniqKey="Lateef M">M. Lateef</name></author><author><name sortKey="Iqbal, L" uniqKey="Iqbal L">L. Iqbal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nkengfack, A E" uniqKey="Nkengfack A">A. E. Nkengfack</name></author><author><name sortKey="Azebaze, A G B" uniqKey="Azebaze A">A. G. B. Azebaze</name></author><author><name sortKey="Waffo, A K" uniqKey="Waffo A">A. K. Waffo</name></author><author><name sortKey="Fomum, Z T" uniqKey="Fomum Z">Z. T. Fomum</name></author><author><name sortKey="Meyer, M" uniqKey="Meyer M">M. Meyer</name></author><author><name sortKey="Van Heerden, F R" uniqKey="Van Heerden F">F. R. Van Heerden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nwodo, J N" uniqKey="Nwodo J">J. N. Nwodo</name></author><author><name sortKey="Ibezim, A" uniqKey="Ibezim A">A. Ibezim</name></author><author><name sortKey="Simoben, C V" uniqKey="Simoben C">C. V. Simoben</name></author><author><name sortKey="Ntie Kang, F" uniqKey="Ntie Kang F">F. Ntie-Kang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nyandoro, S S" uniqKey="Nyandoro S">S. S. Nyandoro</name></author><author><name sortKey="Munissi, J J E" uniqKey="Munissi J">J. J. E. Munissi</name></author><author><name sortKey="Kombo, M" uniqKey="Kombo M">M. Kombo</name></author><author><name sortKey="Mgina, C A" uniqKey="Mgina C">C. A. Mgina</name></author><author><name sortKey="Pan, F" uniqKey="Pan F">F. Pan</name></author><author><name sortKey="Gruhonjic, A" uniqKey="Gruhonjic A">A. Gruhonjic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oakley, R H" uniqKey="Oakley R">R. H. Oakley</name></author><author><name sortKey="Cidlowski, J A" uniqKey="Cidlowski J">J. A. Cidlowski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ocloo, A" uniqKey="Ocloo A">A. Ocloo</name></author><author><name sortKey="Kingsford Adaboh, R" uniqKey="Kingsford Adaboh R">R. Kingsford-Adaboh</name></author><author><name sortKey="Murray, A J" uniqKey="Murray A">A. J. Murray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oh, W K" uniqKey="Oh W">W. K. Oh</name></author><author><name sortKey="Lee, C H" uniqKey="Lee C">C. H. Lee</name></author><author><name sortKey="Seo, J H" uniqKey="Seo J">J. H. Seo</name></author><author><name sortKey="Chung, M Y" uniqKey="Chung M">M. Y. Chung</name></author><author><name sortKey="Cui, L" uniqKey="Cui L">L. Cui</name></author><author><name sortKey="Fomum, Z T" uniqKey="Fomum Z">Z. T. Fomum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oh, W K" uniqKey="Oh W">W. K. Oh</name></author><author><name sortKey="Kim, B Y" uniqKey="Kim B">B. Y. Kim</name></author><author><name sortKey="Oh, H" uniqKey="Oh H">H. Oh</name></author><author><name sortKey="Kim, B S" uniqKey="Kim B">B. S. Kim</name></author><author><name sortKey="Ahn, J S" uniqKey="Ahn J">J. S. Ahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okamoto, Y" uniqKey="Okamoto Y">Y. Okamoto</name></author><author><name sortKey="Suzuki, A" uniqKey="Suzuki A">A. Suzuki</name></author><author><name sortKey="Ueda, K" uniqKey="Ueda K">K. Ueda</name></author><author><name sortKey="Ito, C" uniqKey="Ito C">C. Ito</name></author><author><name sortKey="Itoigawa, M" uniqKey="Itoigawa M">M. Itoigawa</name></author><author><name sortKey="Furukawa, H" uniqKey="Furukawa H">H. Furukawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patil, V M" uniqKey="Patil V">V. M. Patil</name></author><author><name sortKey="Masand, N" uniqKey="Masand N">N. Masand</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perese, D A" uniqKey="Perese D">D. A. Perese</name></author><author><name sortKey="Ulman, J" uniqKey="Ulman J">J. Ulman</name></author><author><name sortKey="Viola, J" uniqKey="Viola J">J. Viola</name></author><author><name sortKey="Ewing, S E E" uniqKey="Ewing S">S. E. E. Ewing</name></author><author><name sortKey="Bankiewicz, K S" uniqKey="Bankiewicz K">K. S. Bankiewicz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Power, O" uniqKey="Power O">O. Power</name></author><author><name sortKey="Jakeman, P" uniqKey="Jakeman P">P. Jakeman</name></author><author><name sortKey="Fitzgerald, R J" uniqKey="Fitzgerald R">R. J. FitzGerald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prior, R L" uniqKey="Prior R">R. L. Prior</name></author><author><name sortKey="Wu, X" uniqKey="Wu X">X. Wu</name></author><author><name sortKey="Schaich, K" uniqKey="Schaich K">K. Schaich</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahman, M Z" uniqKey="Rahman M">M. Z. Rahman</name></author><author><name sortKey="Rahman, M S" uniqKey="Rahman M">M. S. Rahman</name></author><author><name sortKey="Kaisar, A" uniqKey="Kaisar A">A. Kaisar</name></author><author><name sortKey="Hossain, A" uniqKey="Hossain A">A. Hossain</name></author><author><name sortKey="Rashid, M A" uniqKey="Rashid M">M. A. Rashid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rani, K" uniqKey="Rani K">K. Rani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reynaud, J" uniqKey="Reynaud J">J. Reynaud</name></author><author><name sortKey="Guilet, D" uniqKey="Guilet D">D. Guilet</name></author><author><name sortKey="Terreux, R" uniqKey="Terreux R">R. Terreux</name></author><author><name sortKey="Lussignol, M" uniqKey="Lussignol M">M. Lussignol</name></author><author><name sortKey="Walchshofer, N" uniqKey="Walchshofer N">N. Walchshofer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Riaz, N" uniqKey="Riaz N">N. Riaz</name></author><author><name sortKey="Akram Naveed, M" uniqKey="Akram Naveed M">M. Akram Naveed</name></author><author><name sortKey="Saleem, M" uniqKey="Saleem M">M. Saleem</name></author><author><name sortKey="Jabeen, B" uniqKey="Jabeen B">B. Jabeen</name></author><author><name sortKey="Ashraf, M" uniqKey="Ashraf M">M. Ashraf</name></author><author><name sortKey="Ejaz, S A" uniqKey="Ejaz S">S. A. Ejaz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rios, J L" uniqKey="Rios J">J. L. Ríos</name></author><author><name sortKey="Recio, M C" uniqKey="Recio M">M. C. Recio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rohwer, N" uniqKey="Rohwer N">N. Rohwer</name></author><author><name sortKey="Cramer, T" uniqKey="Cramer T">T. Cramer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="San Martin, A" uniqKey="San Martin A">A. San-Martín</name></author><author><name sortKey="Donoso, V" uniqKey="Donoso V">V. Donoso</name></author><author><name sortKey="Leiva, S" uniqKey="Leiva S">S. Leiva</name></author><author><name sortKey="Bacho, M" uniqKey="Bacho M">M. Bacho</name></author><author><name sortKey="Nu Ez, S" uniqKey="Nu Ez S">S. Núñez</name></author><author><name sortKey="Gutierrez, M" uniqKey="Gutierrez M">M. Gutierrez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sathishkumar, R" uniqKey="Sathishkumar R">R. Sathishkumar</name></author><author><name sortKey="Tharani, R" uniqKey="Tharani R">R. Tharani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schito, L" uniqKey="Schito L">L. Schito</name></author><author><name sortKey="Semenza, G L" uniqKey="Semenza G">G. L. Semenza</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schober, A" uniqKey="Schober A">A. Schober</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sharma, O P" uniqKey="Sharma O">O. P. Sharma</name></author><author><name sortKey="Bhat, T K" uniqKey="Bhat T">T. K. Bhat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shen, B" uniqKey="Shen B">B. Shen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sherif, S H" uniqKey="Sherif S">S. H. Sherif</name></author><author><name sortKey="Vidavalur, S" uniqKey="Vidavalur S">S. Vidavalur</name></author><author><name sortKey="Muralidhar, P" uniqKey="Muralidhar P">P. Muralidhar</name></author><author><name sortKey="Murthy, Y L N" uniqKey="Murthy Y">Y. L. N. Murthy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, L" uniqKey="Shi L">L. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shin, G R" uniqKey="Shin G">G. R. Shin</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S. Lee</name></author><author><name sortKey="Do, S G" uniqKey="Do S">S. G. Do</name></author><author><name sortKey="Shin, E" uniqKey="Shin E">E. Shin</name></author><author><name sortKey="Lee, C H" uniqKey="Lee C">C. H. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Su, Z Q" uniqKey="Su Z">Z. Q. Su</name></author><author><name sortKey="Mo, Z Z" uniqKey="Mo Z">Z. Z. Mo</name></author><author><name sortKey="Liao, J B" uniqKey="Liao J">J. B. Liao</name></author><author><name sortKey="Feng, X X" uniqKey="Feng X">X. X. Feng</name></author><author><name sortKey="Liang, Y Z" uniqKey="Liang Y">Y. Z. Liang</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sudanich, S" uniqKey="Sudanich S">S. Sudanich</name></author><author><name sortKey="Tiyaworanant, S" uniqKey="Tiyaworanant S">S. Tiyaworanant</name></author><author><name sortKey="Yenjai, C" uniqKey="Yenjai C">C. Yenjai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, J B L" uniqKey="Tan J">J. B. L. Tan</name></author><author><name sortKey="Lim, Y Y" uniqKey="Lim Y">Y. Y. Lim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, Y" uniqKey="Tanaka Y">Y. Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tjahjandarie, T S" uniqKey="Tjahjandarie T">T. S. Tjahjandarie</name></author><author><name sortKey="Tanjung, M" uniqKey="Tanjung M">M. Tanjung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tjahjandarie, T S" uniqKey="Tjahjandarie T">T. S. Tjahjandarie</name></author><author><name sortKey="Tanjung, M" uniqKey="Tanjung M">M. Tanjung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tong, J" uniqKey="Tong J">J. Tong</name></author><author><name sortKey="Rathitharan, G" uniqKey="Rathitharan G">G. Rathitharan</name></author><author><name sortKey="Meyer, J H" uniqKey="Meyer J">J. H. Meyer</name></author><author><name sortKey="Furukawa, Y" uniqKey="Furukawa Y">Y. Furukawa</name></author><author><name sortKey="Ang, L C" uniqKey="Ang L">L. C. Ang</name></author><author><name sortKey="Boileau, I" uniqKey="Boileau I">I. Boileau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Trinh, B T D" uniqKey="Trinh B">B. T. D. Trinh</name></author><author><name sortKey="J Ger, A K" uniqKey="J Ger A">A. K. Jäger</name></author><author><name sortKey="Staerk, D" uniqKey="Staerk D">D. Staerk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uddin, M M N" uniqKey="Uddin M">M. M. N. Uddin</name></author><author><name sortKey="Emran, T B" uniqKey="Emran T">T. B. Emran</name></author><author><name sortKey="Mahib, M M R" uniqKey="Mahib M">M. M. R. Mahib</name></author><author><name sortKey="Dash, R" uniqKey="Dash R">R. Dash</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van De Laar, F A" uniqKey="Van De Laar F">F. A. van de Laar</name></author><author><name sortKey="Lucassen, P L" uniqKey="Lucassen P">P. L. Lucassen</name></author><author><name sortKey="Akkermans, R P" uniqKey="Akkermans R">R. P. Akkermans</name></author><author><name sortKey="De Lisdonk, E H" uniqKey="De Lisdonk E">E. H. de Lisdonk</name></author><author><name sortKey="Rutten, G E" uniqKey="Rutten G">G. E. Rutten</name></author><author><name sortKey="Van Weel, C" uniqKey="Van Weel C">C. Van Weel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Tonder, A" uniqKey="Van Tonder A">A. van Tonder</name></author><author><name sortKey="Joubert, A M" uniqKey="Joubert A">A. M. Joubert</name></author><author><name sortKey="Cromarty, A D" uniqKey="Cromarty A">A. D. Cromarty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Venturelli, S" uniqKey="Venturelli S">S. Venturelli</name></author><author><name sortKey="Burkard, M" uniqKey="Burkard M">M. Burkard</name></author><author><name sortKey="Biendl, M" uniqKey="Biendl M">M. Biendl</name></author><author><name sortKey="Lauer, U M" uniqKey="Lauer U">U. M. Lauer</name></author><author><name sortKey="Frank, J" uniqKey="Frank J">J. Frank</name></author><author><name sortKey="Busch, C" uniqKey="Busch C">C. Busch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waffo, A K" uniqKey="Waffo A">A. K. Waffo</name></author><author><name sortKey="Azebaze, G A" uniqKey="Azebaze G">G. A. Azebaze</name></author><author><name sortKey="Nkengfack, A E" uniqKey="Nkengfack A">A. E. Nkengfack</name></author><author><name sortKey="Fomum, Z T" uniqKey="Fomum Z">Z. T. Fomum</name></author><author><name sortKey="Meyer, M" uniqKey="Meyer M">M. Meyer</name></author><author><name sortKey="Bodo, B" uniqKey="Bodo B">B. Bodo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walle, T" uniqKey="Walle T">T. Walle</name></author><author><name sortKey="Ta, N" uniqKey="Ta N">N. Ta</name></author><author><name sortKey="Kawamori, T" uniqKey="Kawamori T">T. Kawamori</name></author><author><name sortKey="Wen, X" uniqKey="Wen X">X. Wen</name></author><author><name sortKey="Tsuji, P A" uniqKey="Tsuji P">P. A. Tsuji</name></author><author><name sortKey="Walle, U K" uniqKey="Walle U">U. K. Walle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L J" uniqKey="Wang L">L. J. Wang</name></author><author><name sortKey="Jiang, B" uniqKey="Jiang B">B. Jiang</name></author><author><name sortKey="Wu, N" uniqKey="Wu N">N. Wu</name></author><author><name sortKey="Wang, S Y" uniqKey="Wang S">S. Y. Wang</name></author><author><name sortKey="Shi, D Y" uniqKey="Shi D">D. Y. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, S Y" uniqKey="Wang S">S. Y. Wang</name></author><author><name sortKey="Sun, Z L" uniqKey="Sun Z">Z. L. Sun</name></author><author><name sortKey="Liu, T" uniqKey="Liu T">T. Liu</name></author><author><name sortKey="Gibbons, S" uniqKey="Gibbons S">S. Gibbons</name></author><author><name sortKey="Zhang, W J" uniqKey="Zhang W">W. J. Zhang</name></author><author><name sortKey="Qing, M" uniqKey="Qing M">M. Qing</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, T" uniqKey="Wang T">T. Wang</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Chu, L" uniqKey="Chu L">L. Chu</name></author><author><name sortKey="Wu, T" uniqKey="Wu T">T. Wu</name></author><author><name sortKey="You, J" uniqKey="You J">J. You</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J. Liu</name></author><author><name sortKey="Pang, Q" uniqKey="Pang Q">Q. Pang</name></author><author><name sortKey="Tao, D" uniqKey="Tao D">D. Tao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, T" uniqKey="Wang T">T. Wang</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y. Liu</name></author><author><name sortKey="Li, X" uniqKey="Li X">X. Li</name></author><author><name sortKey="Xu, Q" uniqKey="Xu Q">Q. Xu</name></author><author><name sortKey="Feng, Y" uniqKey="Feng Y">Y. Feng</name></author><author><name sortKey="Yang, S" uniqKey="Yang S">S. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, P" uniqKey="Wang P">P. Wang</name></author><author><name sortKey="Henning, S M" uniqKey="Henning S">S. M. Henning</name></author><author><name sortKey="Heber, D" uniqKey="Heber D">D. Heber</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Xin, L T" uniqKey="Xin L">L. T. Xin</name></author><author><name sortKey="Yue, S J" uniqKey="Yue S">S. J. Yue</name></author><author><name sortKey="Fan, Y C" uniqKey="Fan Y">Y. C. Fan</name></author><author><name sortKey="Wu, J S" uniqKey="Wu J">J. S. Wu</name></author><author><name sortKey="Yan, D" uniqKey="Yan D">D. Yan</name></author><author><name sortKey="Guan, H S" uniqKey="Guan H">H. S. Guan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiong, W Y" uniqKey="Xiong W">W. Y. Xiong</name></author><author><name sortKey="Wang, J Z" uniqKey="Wang J">J. Z. Wang</name></author><author><name sortKey="Shi, T D" uniqKey="Shi T">T. D. Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, X" uniqKey="Yang X">X. Yang</name></author><author><name sortKey="Jiang, Y" uniqKey="Jiang Y">Y. Jiang</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J. Yang</name></author><author><name sortKey="He, J" uniqKey="He J">J. He</name></author><author><name sortKey="Sun, J" uniqKey="Sun J">J. Sun</name></author><author><name sortKey="Chen, F" uniqKey="Chen F">F. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeh, C H" uniqKey="Yeh C">C. H. Yeh</name></author><author><name sortKey="Yang, J J" uniqKey="Yang J">J. J. Yang</name></author><author><name sortKey="Yang, M L" uniqKey="Yang M">M. L. Yang</name></author><author><name sortKey="Li, Y C" uniqKey="Li Y">Y. C. Li</name></author><author><name sortKey="Kuan, Y H" uniqKey="Kuan Y">Y. H. Kuan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yin, J" uniqKey="Yin J">J. Yin</name></author><author><name sortKey="Han, L" uniqKey="Han L">L. Han</name></author><author><name sortKey="Cong, W" uniqKey="Cong W">W. Cong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, B" uniqKey="Zhang B">B. Zhang</name></author><author><name sortKey="Fan, X" uniqKey="Fan X">X. Fan</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z. Wang</name></author><author><name sortKey="Zhu, W" uniqKey="Zhu W">W. Zhu</name></author><author><name sortKey="Li, J" uniqKey="Li J">J. Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, M" uniqKey="Zhang M">M. Zhang</name></author><author><name sortKey="Qiu, Q" uniqKey="Qiu Q">Q. Qiu</name></author><author><name sortKey="Li, Z" uniqKey="Li Z">Z. Li</name></author><author><name sortKey="Sachdeva, M" uniqKey="Sachdeva M">M. Sachdeva</name></author><author><name sortKey="Min, H" uniqKey="Min H">H. Min</name></author><author><name sortKey="Cardona, D M" uniqKey="Cardona D">D. M. Cardona</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, Z P" uniqKey="Zheng Z">Z. P. Zheng</name></author><author><name sortKey="Tan, H Y" uniqKey="Tan H">H. Y. Tan</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J. Chen</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Pharmacol</journal-id><journal-id journal-id-type="iso-abbrev">Front Pharmacol</journal-id><journal-id journal-id-type="publisher-id">Front. Pharmacol.</journal-id><journal-title-group><journal-title>Frontiers in Pharmacology</journal-title></journal-title-group><issn pub-type="epub">1663-9812</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31551770</article-id><article-id pub-id-type="pmc">6746831</article-id><article-id pub-id-type="doi">10.3389/fphar.2019.00952</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pharmacology</subject><subj-group><subject>Review</subject></subj-group></subj-group></article-categories><title-group><article-title>A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ateba</surname><given-names>Sylvin Benjamin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/689006"></uri></contrib><contrib contrib-type="author"><name><surname>Mvondo</surname><given-names>Marie Alfrede</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/689345"></uri></contrib><contrib contrib-type="author"><name><surname>Djiogue</surname><given-names>Sefirin</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zingué</surname><given-names>Stéphane</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/690984"></uri></contrib><contrib contrib-type="author"><name><surname>Krenn</surname><given-names>Liselotte</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/25366"></uri></contrib><contrib contrib-type="author"><name><surname>Njamen</surname><given-names>Dieudonné</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><uri xlink:type="simple" xlink:href="https://loop.frontiersin.org/people/690139"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Laboratory of Animal Physiology, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé I</institution>,<addr-line>Yaoundé</addr-line>,<country>Cameroon</country></aff><aff id="aff2"><sup>2</sup><institution>Research Unit of Animal Physiology and Phytopharmacology, Department of Animal Biology, Faculty of Science, University of Dschang</institution>,<addr-line>Dschang</addr-line>,<country>Cameroon</country></aff><aff id="aff3"><sup>3</sup><institution>Department of Life and Earth Sciences, Higher Teachers’ Training College, University of Maroua</institution>,<addr-line>Maroua</addr-line>,<country>Cameroon</country></aff><aff id="aff4"><sup>4</sup><institution>Department of Pharmacognosy, University of Vienna, Vienna</institution>,<country>Austria</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Namrita Lall, University of Pretoria, South Africa</p></fn><fn fn-type="edited-by"><p>Reviewed by: Souaibou Yaouba, Université de Lorraine, France; Chi-Rei Wu, China Medical University, Taiwan</p></fn><corresp id="fn001">*Correspondence: Sylvin Benjamin Ateba, <email xlink:href="mailto:s.benjaminateba@gmail.com" xlink:type="simple">s.benjaminateba@gmail.com</email>; Liselotte Krenn, <email xlink:href="mailto:liselotte.krenn@univie.ac.at" xlink:type="simple">liselotte.krenn@univie.ac.at</email></corresp><fn fn-type="other" id="fn002"><p>This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology</p></fn></author-notes><pub-date pub-type="epub"><day>10</day><month>9</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>10</volume><elocation-id>952</elocation-id><history><date date-type="received"><day>25</day><month>2</month><year>2019</year></date><date date-type="accepted"><day>26</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>Copyright © 2019 Ateba, Mvondo, Djiogue, Zingué, Krenn and Njamen</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Ateba, Mvondo, Djiogue, Zingué, Krenn and Njamen</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective nonprenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological effects (therapeutic potential). In this review, we summarize the current information on health-promoting properties of AIF. Reported data evidenced that AIF has a multitherapeutic potential with antiosteoporotic, antioxidant and anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective properties. However, research on these aspects of AIF is not sufficient and needs to be reevaluated using more appropriate methods and methodology. Further series of studies are needed to confirm these pharmacological effects, and this review should lay the basis for the design of respective investigations. Overall, despite the drawbacks of studies recorded, AIF exhibits a potential as drug candidate.</p></abstract><kwd-group><kwd>alpinumisoflavone</kwd><kwd>therapeutic potential</kwd><kwd>natural product</kwd><kwd>prenylated isoflavonoid</kwd><kwd>structure–activity relationship</kwd></kwd-group><funding-group><award-group><funding-source id="cn001">Universität Wien<named-content content-type="fundref-id">10.13039/501100003065</named-content></funding-source></award-group></funding-group><counts><fig-count count="2"></fig-count><table-count count="4"></table-count><equation-count count="0"></equation-count><ref-count count="150"></ref-count><page-count count="19"></page-count><word-count count="9619"></word-count></counts></article-meta></front><body><sec sec-type="intro" id="s1"><title>Introduction</title><p>In the drug discovery process, plants still remain an invaluable source of drugs and drug leads. They possess enormous structural and chemical diversity that is not matched by any synthetic libraries of small molecules (<xref rid="B118" ref-type="bibr">Shen, 2015</xref>). As pharmacological activities of chemicals are generally structure dependent, the structural and chemical diversity is obviously an advantage. Over the last decade, the interest in (iso)flavonoids strongly increased. Especially the prenylated forms moved into the focus because of their versatile and promising pharmacological properties and health benefits on multitarget tissues (<xref rid="B60" ref-type="bibr">Kumar and Pandey, 2013</xref>; <xref rid="B17" ref-type="bibr">Chen et al., 2014</xref>). Prenylated isoflavonoids have increased lipophilicity as compared to nonprenylated forms, leading to high affinity with cell membranes and enhanced biological activities or significant pharmacological effects (<xref rid="B17" ref-type="bibr">Chen et al., 2014</xref>; <xref rid="B119" ref-type="bibr">Sherif et al., 2015</xref>). These compounds offer a multitude of biological activities, which justify major and much deeper pharmacological investigation (<xref rid="B12" ref-type="bibr">Botta et al., 2009</xref>). Accordingly, there is a recent in-depth investigation of prenylated flavonoids as promising anticancer, anti-inflammatory, antioxidant, and neuroprotective nutraceuticals (<xref rid="B145" ref-type="bibr">Yang et al., 2015</xref>; <xref rid="B133" ref-type="bibr">Venturelli et al., 2016</xref>), with the prenyl substituent playing a key role in the molecular activity. Prenylated flavonoids are found predominantly in the Leguminosae family, although the phenyl-propanoid pathway—necessary for their production—is ubiquitously present in plants including nonleguminous families (<xref rid="B109" ref-type="bibr">Reynaud et al., 2005</xref>; <xref rid="B64" ref-type="bibr">Lapčík, 2007</xref>).</p><p>Alpinumisoflavone (AIF) or [5-hydroxy-7-(p-hydroxyphenyl)-2,2-dimethyl-2H-6H-benzo-[1,2-b:5,4-b]dipyran-6-one] is a dimethylpyrano derivative prenylated at ring A of genistein (<xref ref-type="fig" rid="f1"><bold>Figure 1</bold></xref>). It is a major constituent of <italic>Derris eriocarpa</italic> F.C. How, commonly referred as “Tugancao” in “Zhuang” and “Dai” ethnomedicine in Guangxi and Yunnan Province of China (<xref rid="B42" ref-type="bibr">Guangxi Institute of Chinese Medicine, 1986</xref>). A high content of AIF was reported in fully mature fruits (mandarin melon berry) of <italic>Cudrania tricuspidata</italic> Bur. ex Lavallee (syn. <italic>Maclura tricuspidata</italic> Carrière) (<xref rid="B121" ref-type="bibr">Shin et al., 2015</xref>), a crop cultivated in East Asia (<xref rid="B144" ref-type="bibr">Xiong et al., 1993</xref>; <xref rid="B120" ref-type="bibr">Shi, 2010</xref>), Europe and America (<xref rid="B80" ref-type="bibr">Markovski, 2016</xref>) for its fruits and timber, and with an immense medicinal and economic value (<xref rid="B143" ref-type="bibr">Xin et al., 2017</xref>). Isolated for the first time by <xref rid="B53" ref-type="bibr">Jackson et al. (1971)</xref>, AIF was identified in many medicinal plants widely used over the world (<xref rid="T1" ref-type="table"><bold>Table 1</bold></xref>). Although data depicted in this table are not exhaustive, the global trend is in accordance with <xref rid="B13" ref-type="bibr">Botta et al. (2005)</xref> who reported that prenylated flavonoids occur mostly in Leguminosae and Moraceae, with few detected in other families. Over the last two decades, the body of literature of AIF and its pharmacological potential is steadily growing. This review summarizes and gives a critical look on the current knowledge of the biological activities, therapeutic potential, and mechanism of action of AIF.</p><fig id="f1" position="float"><label>Figure 1</label><caption><p>Chemical structures of isoflavone, genistein, alpinumisoflavone, and some of its derivatives.</p></caption><graphic xlink:href="fphar-10-00952-g001"></graphic></fig><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Sources and biological and/or pharmacological activities of alpinumisoflavone.</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" rowspan="1" colspan="1">Family</th><th valign="top" rowspan="1" colspan="1">Plant species</th><th valign="top" rowspan="1" colspan="1">Plant parts</th><th valign="top" rowspan="1" colspan="1">Origin/city (country)</th><th valign="top" rowspan="1" colspan="1">Biological and/or pharmacological activity</th><th valign="top" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td valign="top" rowspan="1" colspan="1"><bold>Leguminosae</bold></td><td valign="top" rowspan="1" colspan="1"><italic>Crotalaria bracteata</italic></td><td valign="top" rowspan="1" colspan="1">Roots and stems</td><td valign="top" rowspan="1" colspan="1">Roi-Et<break></break>(Thailand)</td><td valign="top" rowspan="1" colspan="1">Cytotoxicity against MCF-7 and NCI-H187 cell lines (inactive)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B123" ref-type="bibr">Sudanich et al., 2017</xref></td></tr><tr><td valign="top" rowspan="13" colspan="1"></td><td valign="top" rowspan="1" colspan="1"><italic>Erythrina caffra</italic> Thunb.</td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">KwaZulu-Natal<break></break>(South Africa)</td><td valign="top" rowspan="1" colspan="1">Anti-bacterial activity against <italic>Staphylococcus aureus</italic>, <italic>Bacillus subtilis</italic>, <italic>Klebsiella pneumonia</italic> and <italic>Escherichia coli</italic></td><td valign="top" rowspan="1" colspan="1"><xref rid="B18" ref-type="bibr">Chukwujekwu et al., 2011</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina indica</italic></td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Ibadan (Nigeria)</td><td valign="top" rowspan="1" colspan="1"><italic>C</italic>ytotoxicity against KB cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B95" ref-type="bibr">Nkengfack et al., 2001</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina lysistemon</italic></td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">–<break></break>(Zimbabwe)</td><td valign="top" rowspan="1" colspan="1">Estrogen-like effects in a menopause model of<break></break>ovariectomized Wistar rats</td><td valign="top" rowspan="1" colspan="1"><xref rid="B86" ref-type="bibr">Mvondo et al., 2011</xref>; <xref rid="B85" ref-type="bibr">Mvondo et al., 2012</xref>; <xref rid="B87" ref-type="bibr">Mvondo et al., 2015</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina mildbraedii</italic></td><td valign="top" rowspan="1" colspan="1">Root bark</td><td valign="top" rowspan="1" colspan="1">Buea<break></break>(Cameroon)</td><td valign="top" rowspan="1" colspan="1">Inhibition of protein tyrosine phosphatase-1B (PTP1B)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B88" ref-type="bibr">Na et al., 2006</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina orientalis</italic></td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Kunir Kidul (Indonesia)</td><td valign="top" rowspan="1" colspan="1">Cytotoxicity against murine leukemia P-388 cells<break></break>Radical scavenging activity using DPPH (2,2-diphenyl-1-picrylhydrazyl)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina ovalifolia</italic> Roxb.</td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Kunir Kidul (Indonesia)</td><td valign="top" rowspan="1" colspan="1">Antiplasmodial activity against <italic>Plasmodium falciparum</italic></td><td valign="top" rowspan="1" colspan="1"><xref rid="B127" ref-type="bibr">Tjahjandarie and Tanjung, 2015b</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina poeppigiana</italic></td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Sancta Cruz (Bolivia)</td><td valign="top" rowspan="1" colspan="1">Estrogen-like effect in U2OS human osteosarcoma cells through ERs-dependent reporter gene activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B33" ref-type="bibr">Djiogue et al., 2009</xref>; <xref rid="B34" ref-type="bibr">Djiogue et al., 2010</xref></td></tr><tr><td valign="top" rowspan="3" colspan="1"><italic>Erythrina senegalensis</italic> DC</td><td valign="top" rowspan="3" colspan="1">Stem bark</td><td valign="top" rowspan="3" colspan="1">Foumban (Cameroon)</td><td valign="top" rowspan="1" colspan="1">Inhibition of the HIV-1 Protease</td><td valign="top" rowspan="1" colspan="1"><xref rid="B65" ref-type="bibr">Lee et al., 2009a</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Phospholipase Cγ1inhibitory activity (inactive)<break></break>Inhibition of acyl CoA:diacylglycerol acyltransferase</td><td valign="top" rowspan="1" colspan="1"><xref rid="B101" ref-type="bibr">Oh et al., 2005</xref><break></break><xref rid="B100" ref-type="bibr">Oh et al., 2009</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1"></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina stricta</italic> Roxb.</td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Nagaland<break></break>(India)</td><td valign="top" rowspan="1" colspan="1">Antimicrobial and radical scavenging (DPPH) activities</td><td valign="top" rowspan="1" colspan="1"><xref rid="B1" ref-type="bibr">Akter et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina suberosa</italic> Roxb.</td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Jammu<break></break>(India)</td><td valign="top" rowspan="1" colspan="1">Cytotoxicity against human myeloid leukemia cell lines HL-60 and K-562 and T lymphoblastic cell line MOLT-4<break></break>Apoptotic potential in HL-60 cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B61" ref-type="bibr">Kumar et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Erythrina variegate</italic> L.</td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Dhaka<break></break>(Bangladesh)</td><td valign="top" rowspan="1" colspan="1">Radical scavenging (DPPH) activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B107" ref-type="bibr">Rahman et al., 2010</xref></td></tr><tr><td valign="top" rowspan="11" colspan="1"><bold>Leguminosae</bold></td><td valign="top" rowspan="2" colspan="1"><italic>Derris eriocarpa</italic></td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">Inhibition of osteoclast differentiation in vitro and antiosteoporotic effect in ovariectomized mice</td><td valign="top" rowspan="1" colspan="1"><xref rid="B28" ref-type="bibr">Cong et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">Suppression of tumor growth and metastasis of clear-cell renal cell carcinoma</td><td valign="top" rowspan="1" colspan="1"><xref rid="B138" ref-type="bibr">Wang et al., 2017a</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Laburnum alpinum</italic> J. Presl.</td><td valign="top" rowspan="1" colspan="1">Twigs</td><td valign="top" rowspan="1" colspan="1">Salford<break></break>(England)</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1"><xref rid="B53" ref-type="bibr">Jackson et al., 1971</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Lonchocarpus glabrescens</italic></td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">Punchana, (Peru)</td><td valign="top" rowspan="1" colspan="1">Inhibition of the hypoxia-inducible factor-1 (HIF-1) activation in human breast tumor T47D cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B75" ref-type="bibr">Liu et al., 2009</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Milletia pachycarpa</italic></td><td valign="top" rowspan="1" colspan="1">Stem and leaves</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">No estrogenic activity on the β-galactosidase activity in a yeast two-hybrid assay</td><td valign="top" rowspan="1" colspan="1"><xref rid="B102" ref-type="bibr">Okamoto et al., 2006</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Millettia taiwaniana</italic></td><td valign="top" rowspan="1" colspan="1">Twigs and leaves</td><td valign="top" rowspan="1" colspan="1">–<break></break>(Singapore)</td><td valign="top" rowspan="1" colspan="1">Inhibition of the Epstein–Barr virus activation with no cytotoxicity against Raji cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B52" ref-type="bibr">Ito et al., 2000</xref></td></tr><tr><td valign="top" rowspan="3" colspan="1"><italic>Millettia thonningii</italic> (Schum. et Thonn.) Bak.</td><td valign="top" rowspan="1" colspan="1">Seeds</td><td valign="top" rowspan="1" colspan="1">Legon-Accra<break></break>(Ghana)</td><td valign="top" rowspan="1" colspan="1">Antifungal activity against wild-type <italic>Candida albicans</italic> and the reference strain ATCC18804C</td><td valign="top" rowspan="1" colspan="1"><xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Seeds</td><td valign="top" rowspan="1" colspan="1">Accra<break></break>(Ghana)</td><td valign="top" rowspan="1" colspan="1">Antischistosomal activity against <italic>Schistosoma mansoni</italic></td><td valign="top" rowspan="1" colspan="1"><xref rid="B76" ref-type="bibr">Lyddiard et al., 2002</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Seeds</td><td valign="top" rowspan="1" colspan="1">–<break></break>(Ghana)</td><td valign="top" rowspan="1" colspan="1">Antiplasmodial activity against <italic>Plasmodium falciparum</italic></td><td valign="top" rowspan="1" colspan="1"><xref rid="B56" ref-type="bibr">Khalid et al., 1986</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Sophora moorcroftiana</italic> (Wall.)</td><td valign="top" rowspan="1" colspan="1">Aerial parts</td><td valign="top" rowspan="1" colspan="1">Tibet<break></break>(China)</td><td valign="top" rowspan="1" colspan="1">Antibacterial effects on Meticillin-resistant <italic>Staphylococcus aureus</italic></td><td valign="top" rowspan="1" colspan="1"><xref rid="B137" ref-type="bibr">Wang et al., 2014</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Tipuana tipu</italic> (Benth.)<break></break>Lillo</td><td valign="top" rowspan="1" colspan="1">Leaves</td><td valign="top" rowspan="1" colspan="1">Mansoura (Egypt)</td><td valign="top" rowspan="1" colspan="1">Antiproliferative activity against leukemia [CCRF-CEM, MOLT-4, and HL-60(TB)], renal SN12C, and breast MCF-7 cancer cells<break></break>Anti-inflammatory activity in carrageenan-induced rat paw edema model</td><td valign="top" rowspan="1" colspan="1"><xref rid="B3" ref-type="bibr">Amen et al., 2013</xref></td></tr><tr><td valign="top" rowspan="11" colspan="1"><bold>Moraceae</bold></td><td valign="top" rowspan="1" colspan="1"><italic>Chlorophora tinctoria</italic> (L.) Gaud.</td><td valign="top" rowspan="1" colspan="1">Leaves and twigs</td><td valign="top" rowspan="1" colspan="1">Maynas<break></break>(Peru)</td><td valign="top" rowspan="1" colspan="1">Fatty acid synthase inhibitory and antifungal activities (inactive)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B73" ref-type="bibr">Li et al., 2002</xref></td></tr><tr><td valign="top" rowspan="2" colspan="1"><italic>Cudrania tricuspidata</italic> (Carr.)</td><td valign="top" rowspan="1" colspan="1">Fruits</td><td valign="top" rowspan="1" colspan="1">Cheongju, (Korea)</td><td valign="top" rowspan="1" colspan="1">Inhibition of the mouse brain monoamine oxidase</td><td valign="top" rowspan="1" colspan="1"><xref rid="B43" ref-type="bibr">Han et al., 2005</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Twigs</td><td valign="top" rowspan="1" colspan="1">Anhui (China)</td><td valign="top" rowspan="1" colspan="1">Tyrosinase inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B150" ref-type="bibr">Zheng et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus bengalensis</italic></td><td valign="top" rowspan="1" colspan="1">Aerial roots</td><td valign="top" rowspan="1" colspan="1">Sahiwal (Punjab, India)</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1"><xref rid="B110" ref-type="bibr">Riaz et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus benjamina</italic> var. nuda (Miq.) Barrett</td><td valign="top" rowspan="1" colspan="1">Fruits</td><td valign="top" rowspan="1" colspan="1">Honolulu (Hawaii)</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1"><xref rid="B30" ref-type="bibr">Dai et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus chlamydocarpa</italic> Mildbraed and Burret</td><td valign="top" rowspan="1" colspan="1">Root bark<break></break></td><td valign="top" rowspan="1" colspan="1">Bahouan<break></break>(Cameroon)</td><td valign="top" rowspan="1" colspan="1">Antimycobacterial, antibacterial and antifungal activities</td><td valign="top" rowspan="1" colspan="1"><xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus glumosa</italic></td><td valign="top" rowspan="1" colspan="1">Stem bark</td><td valign="top" rowspan="1" colspan="1">Makenene<break></break>(Cameroon)</td><td valign="top" rowspan="1" colspan="1">Cytotoxicity against prostate cancer PC-3 cell line</td><td valign="top" rowspan="1" colspan="1"><xref rid="B91" ref-type="bibr">Nana et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus nervosa</italic><break></break>Heyne ex Roth.</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Pingtung (Taiwan)</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1"><xref rid="B16" ref-type="bibr">Chen et al., 2010</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus racemosa</italic></td><td valign="top" rowspan="1" colspan="1">Fruits</td><td valign="top" rowspan="1" colspan="1">–<break></break>(Vietnam)</td><td valign="top" rowspan="1" colspan="1">Inhibition of protein tyrosine phosphatase-1B (PTP1B)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B129" ref-type="bibr">Trinh et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Ficus tikoua</italic> Bur</td><td valign="top" rowspan="1" colspan="1"><italic>Rhizomes</italic></td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Radical scavenging (DPPH) and α-glucosidase inhibitory activities</td><td valign="top" rowspan="1" colspan="1"><xref rid="B40" ref-type="bibr">Fu et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Maclura tricuspidata</italic> Carrière (syn.<italic>Cudrania tricuspidata</italic>)</td><td valign="top" rowspan="1" colspan="1">Fruits</td><td valign="top" rowspan="1" colspan="1">Jinju<break></break>(South Korea)</td><td valign="top" rowspan="1" colspan="1">Cytotoxicity against human neuroblastoma SH-SY5Y cell line</td><td valign="top" rowspan="1" colspan="1"><xref rid="B49" ref-type="bibr">Hong et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>Dilleniaceae</bold></td><td valign="top" rowspan="1" colspan="1"><italic>Tetracera scandens</italic></td><td valign="top" rowspan="1" colspan="1">Branch</td><td valign="top" rowspan="1" colspan="1">–<break></break>(Vietnam)</td><td valign="top" rowspan="1" colspan="1">Glucose-uptake induced activity in basal and insulin-stimulated L6 myotubes</td><td valign="top" rowspan="1" colspan="1"><xref rid="B66" ref-type="bibr">Lee et al., 2009b</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>Apiaceae</bold></td><td valign="top" rowspan="1" colspan="1"><italic>Azorella madreporica</italic></td><td valign="top" rowspan="1" colspan="1">Whole plant</td><td valign="top" rowspan="1" colspan="1">Valle Nevado (Chile)</td><td valign="top" rowspan="1" colspan="1">Antimycobacterial and antibacterial activities (inactive)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B113" ref-type="bibr">San-Martín et al., 2015</xref></td></tr></tbody></table><table-wrap-foot><p>–‚ not indicated.</p></table-wrap-foot></table-wrap></sec><sec id="s2"><title>Pharmacological Activities</title><p>Over the last decade research indicates that prenylation usually renders (iso)flavonoids with improved bioactivities (<xref rid="B145" ref-type="bibr">Yang et al., 2015</xref>; <xref rid="B84" ref-type="bibr">Mukai, 2018</xref>), suggesting that prenylated compounds have a higher potential to be developed and utilized (<xref rid="B17" ref-type="bibr">Chen et al., 2014</xref>). Focusing on AIF, the following activities have been demonstrated and claimed to be promising by the authors (<xref rid="T2" ref-type="table"><bold>Table 2</bold></xref>).</p><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Pharmacological activities of alpinumisoflavone and underlying mechanisms.</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" rowspan="1" colspan="1">Pharmacological activities</th><th valign="top" rowspan="1" colspan="1">Experimental model</th><th valign="top" rowspan="1" colspan="1">Dose/concentration</th><th valign="top" rowspan="1" colspan="1">Mechanism of action</th><th valign="top" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td valign="top" rowspan="7" colspan="1">Estrogenic activity</td><td valign="top" rowspan="1" colspan="1">ER competitor binding assay</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Weak ERα and ERβ binder; higher selectivity for ERα</td><td valign="top" rowspan="1" colspan="1"><xref rid="B85" ref-type="bibr">Mvondo et al., 2012</xref>; <xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">ER competitor binding assay</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Weak ERα and ERβ binder; higher selectivity for ERβ</td><td valign="top" rowspan="1" colspan="1"><xref rid="B33" ref-type="bibr">Djiogue et al., 2009</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">U2OS-ERα, U2OS-ERβ human osteosarcoma cells</td><td valign="top" rowspan="1" colspan="1">10<sup>−9</sup>–10<sup>−6</sup> M</td><td valign="top" rowspan="1" colspan="1">Induction of luciferase reporter gene activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B34" ref-type="bibr">Djiogue et al., 2010</xref>; <xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">MCF-7 breast cancer cells</td><td valign="top" rowspan="1" colspan="1">10<sup>−9</sup>–10<sup>−6</sup> M</td><td valign="top" rowspan="1" colspan="1">Up-regulation of the expression of estrogen α receptor target genes PCNA, cyclin D1, cyclinE1, cMyc, and LRH-1; downregulation of GREB1 at 10<sup>−9</sup> M</td><td valign="top" rowspan="1" colspan="1"><xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Ovariectomized Wistar rats</td><td valign="top" rowspan="1" colspan="1">0.01, 0.1, and 1 mg/kg daily for 3 days i.p.</td><td valign="top" rowspan="1" colspan="1">Increase in uterine wet weight, and uterine and vaginal epithelial height</td><td valign="top" rowspan="1" colspan="1"><xref rid="B85" ref-type="bibr">Mvondo et al., 2012</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Ovariectomized Wistar rats</td><td valign="top" rowspan="1" colspan="1">1, 10 mg/kg daily for 28 days i.p.</td><td valign="top" rowspan="1" colspan="1">Increase in uterine and vaginal epithelial height; increase in FSH/LH ratio;<break></break>reduction in atherogenic risks</td><td valign="top" rowspan="1" colspan="1"><xref rid="B86" ref-type="bibr">Mvondo et al., 2011</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Ovariectomized Wistar rats</td><td valign="top" rowspan="1" colspan="1">0.1, 1, and 10 mg/kg daily for 3 days i.p.</td><td valign="top" rowspan="1" colspan="1">Down-regulation of Esr1 mRNA expression; upregulation of Cyp7a1 mRNA expression.</td><td valign="top" rowspan="1" colspan="1"><xref rid="B87" ref-type="bibr">Mvondo et al., 2015</xref></td></tr><tr><td valign="top" rowspan="4" colspan="1">Antiosteoporotic activity</td><td valign="top" rowspan="1" colspan="1">RAW264.7 osteoclast precursor</td><td valign="top" rowspan="1" colspan="1">2.5 and 5 µM</td><td valign="top" rowspan="1" colspan="1">Suppression of osteoclast differentiation and proliferation by inhibiting RANKL-induced p38, ERK and JNK activation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B28" ref-type="bibr">Cong et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Ovariectomy-induced osteoporosis</td><td valign="top" rowspan="1" colspan="1">10, 25 mg/kg daily for 6 weeks p.o.</td><td valign="top" rowspan="1" colspan="1">Prevention of OVX-induced bone loss by increasing BV/TV ratio, Tb.Th and Tb.N while decreasing Tb.Sp in OVX mice</td><td valign="top" rowspan="1" colspan="1"><xref rid="B28" ref-type="bibr">Cong et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Dexamethasone-induced osteoporosis</td><td valign="top" rowspan="1" colspan="1">20, 40 mg/kg daily for 8 weeks p.o.</td><td valign="top" rowspan="1" colspan="1">Increase in bone mineral density and mineral content of the proximal femur bone in rats; increase in BV/TV ratio, Tb.Th and Tb.N; decrease in Tb.Sp</td><td valign="top" rowspan="1" colspan="1"><xref rid="B139" ref-type="bibr">Wang et al., 2017b</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">MC3T3-E1 and MLO-Y4 osteoblasts and osteocytes</td><td valign="top" rowspan="1" colspan="1">5–20 µM</td><td valign="top" rowspan="1" colspan="1">Reverse of proapoptotic and antiproliferative effects of dexamethasone <italic>via</italic> suppressing Nox2-dependent ROS generation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B139" ref-type="bibr">Wang et al., 2017b</xref>; <xref rid="B147" ref-type="bibr">Yin et al., 2018</xref></td></tr><tr><td valign="top" rowspan="3" colspan="1">Antioxidant activity</td><td valign="top" rowspan="1" colspan="1">DPPH assay</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub>: 8.30 µg/ml<break></break>IC<sub>50</sub>: 708.5 µM<break></break>IC<sub>50</sub>: 54.80 µg/ml IC<sub>50</sub>: 54.02 µg/ml</td><td valign="top" rowspan="1" colspan="1">DPPH scavenging activity of differing degree</td><td valign="top" rowspan="1" colspan="1"><xref rid="B107" ref-type="bibr">Rahman et al., 2010</xref>; <xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref>;<break></break><xref rid="B40" ref-type="bibr">Fu et al., 2018</xref><break></break><xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>;</td></tr><tr><td valign="top" rowspan="1" colspan="1">Ferric Reducing Antioxidant Power (FRAP) assay</td><td valign="top" rowspan="1" colspan="1">35.55 µM trolox equivalents/1.5 mM</td><td valign="top" rowspan="1" colspan="1">Free radical-scavenging activity<break></break>Increase in the FRAP reducing power</td><td valign="top" rowspan="1" colspan="1"><xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>;</td></tr><tr><td valign="top" rowspan="1" colspan="1">LPS-stimulated RAW264.7 cells</td><td valign="top" rowspan="1" colspan="1">5, 10 µg/ml</td><td valign="top" rowspan="1" colspan="1">Increase in catalase, HO-1, glutathione peroxidase, and superoxide dismutase production</td><td valign="top" rowspan="1" colspan="1"><xref rid="B71" ref-type="bibr">Li et al., 2018</xref></td></tr><tr><td valign="top" rowspan="3" colspan="1">Anti-inflammatory activity</td><td valign="top" rowspan="1" colspan="1">LPS-stimulated acute lung injury in mice</td><td valign="top" rowspan="1" colspan="1">1, 5, 10 mg/kg i.p. 1 h before LPS challenge</td><td valign="top" rowspan="1" colspan="1">Alleviated lung lesions, pulmonary edema, and hemorrhages: inhibition of myeloperoxidase activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B71" ref-type="bibr">Li et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">LPS-stimulated RAW264.7 cells</td><td valign="top" rowspan="1" colspan="1">5, 10 µg/ml</td><td valign="top" rowspan="1" colspan="1">Decreased production of TNF-α, IL-6, IL-1b, ICAM-1, and NO; suppression of NF-κB, MAPKs, and NLRP3 pathways</td><td valign="top" rowspan="1" colspan="1"><xref rid="B71" ref-type="bibr">Li et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Carrageenan-induced rat paw edema</td><td valign="top" rowspan="1" colspan="1">25 mg/kg i.p. 30 min before λ-carrageenan (unique dose)</td><td valign="top" rowspan="1" colspan="1">Inhibition of edema formation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B3" ref-type="bibr">Amen et al., 2013</xref></td></tr><tr><td valign="top" rowspan="2" colspan="1">Antimicrobial activity</td><td valign="top" rowspan="1" colspan="1"><italic>Mycobacterium smegmatis</italic> MC2 155</td><td valign="top" rowspan="1" colspan="1">MIC = 19.53 µg/ml<break></break>MBC = 39.06 µg/ml</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Enterobacter cloacae</italic> LMP1104G<break></break><italic>Escherichia coli</italic> LMP0101U<break></break><italic>Morganella morganii</italic> LMP0904G<break></break><italic>Proteus mirabilis</italic> LMP0504G <italic>Staphylococcus aureus</italic> LMP0206U<break></break><italic>Bacillus stearothermophilus</italic> LMP0104G</td><td valign="top" rowspan="1" colspan="1">IZ = 15.5–18.7 mm except for <italic>E. coli</italic> (7 mm)<break></break>MIC = 39.06 µg/ml except for <italic>P. mirabilis</italic> (78.12 µg/ml)</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref></td></tr><tr><td valign="top" rowspan="5" colspan="1"></td><td valign="top" rowspan="1" colspan="1"><italic>Candida albicans</italic></td><td valign="top" rowspan="1" colspan="1">IZ = 14.5 mm<break></break>MIC = 78.12 µg/ml</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Candida albicans</italic> wild type<break></break><italic>Candida albicans</italic> ATCC18804</td><td valign="top" rowspan="1" colspan="1">MIC = 0.25 µg/ml<break></break>MIC = 0.50 µg/ml</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">3D structure of CdsD protein of Chlamydial T3SS</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Interaction with the active site residue GLU-626(O-H) of contact-dependent secretion D (CdsD) protein</td><td valign="top" rowspan="1" colspan="1"><xref rid="B114" ref-type="bibr">Sathishkumar and Tharani, 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Bacillus subtilis</italic> ATCC6051<break></break><italic>Staphylococcus aureus</italic> ATCC12600<break></break><italic>Klebsiella pneumoniae</italic> ATCC 13883<break></break><italic>Escherichia coli</italic> ATCC11775</td><td valign="top" rowspan="1" colspan="1">MIC of 3.9 µg/ml except for <italic>B. subtilis</italic> (7.8 µg/ml)</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B18" ref-type="bibr">Chukwujekwu et al., 2011</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><italic>Staphylococcus aureus</italic> SA1199B<break></break><italic>Staphylococcus aureus</italic> RN4220<break></break><italic>Staphylococcus aureus</italic> EMRSA-15<break></break><italic>Staphylococcus aureus</italic> XU212<break></break><italic>Staphylococcus aureus</italic> EMRSA-16<break></break><italic>Staphylococcus aureus</italic> ATCC25923</td><td valign="top" rowspan="1" colspan="1">MIC = 64 µg/ml<break></break>MIC = 128 µg/ml<break></break>MIC = 128 µg/ml<break></break>MIC > 128 µg/ml<break></break>MIC > 128 µg/ml<break></break>MIC > 128 µg/ml</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B137" ref-type="bibr">Wang et al., 2014</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Antimicrobial activity</td><td valign="top" rowspan="1" colspan="1"><italic>Staphylococcus aureus</italic> MSSA<break></break><italic>Staphylococcus aureus</italic> MRSA<break></break><italic>Staphylococcus aureus</italic> MDRSA</td><td valign="top" rowspan="1" colspan="1">MIC = 15 µg/ml<break></break>MIC = 30 µg/ml<break></break>MIC = 30 µg/ml</td><td valign="top" rowspan="1" colspan="1">Growth inhibition</td><td valign="top" rowspan="1" colspan="1"><xref rid="B1" ref-type="bibr">Akter et al., 2016</xref></td></tr><tr><td valign="top" rowspan="6" colspan="1">Anticancer activity</td><td valign="top" rowspan="1" colspan="1">KB oral epidermoid carcinoma cells</td><td valign="top" rowspan="1" colspan="1">ED<sub>50</sub> = 4.13 µg/ml</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B95" ref-type="bibr">Nkengfack et al., 2001</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">P-388 leukemia cells</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 4.31 µg/ml</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">HL-60, MOLT-4, K-562 leukemia cells</td><td valign="top" rowspan="1" colspan="1">50 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation; induction of apoptosis <italic>via</italic> both intrinsic and extrinsic pathways (activation of caspase-3, -8, -9; PARP cleavage; release of cytochrome c, Bax; downregulation of Bcl-2 expression) and inhibition of NF-kB (p65)/Stat3 tango in HL-60 cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B61" ref-type="bibr">Kumar et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Full NCI 60 cell panel</td><td valign="top" rowspan="1" colspan="1">10<sup>−5</sup> M</td><td valign="top" rowspan="1" colspan="1">Inhibition of proliferation of CCRF-CEM, MOLT-4, and HL-60(TB) leukemia cells, SN12C renal cancer cells and MCF7 breast cancer cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B3" ref-type="bibr">Amen et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">H2108, H1299, MRC-5 lung cancer cells;<break></break>LPS-stimulated RAW264.7 cells</td><td valign="top" rowspan="1" colspan="1">30, 60 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell viability; induction of apoptosis (activation of caspase 3/7; repression of AP-1 and NF-kB-dependent transcription; inhibition of ERK/MAPK pathway);<break></break>Suppression of (LPS)-induced NO productiwn</td><td valign="top" rowspan="1" colspan="1"><xref rid="B89" ref-type="bibr">Namkoong et al., 2011</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Eca109, KYSE30 esophageal squamous carcinoma cells (ESCC);<break></break>Eca109 xenograft mouse model</td><td valign="top" rowspan="1" colspan="1">5, 10, 20 µM;<break></break>20 mg/kg daily for 20 days</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation; increase in radio-sensitivity of ESCC; enhanced irradiation-induced DNA damage, apoptosis, G2/M cell cycle arrest; increase in irradiation-induced ROS generation by suppressing Nrf2 and target genes HO-1 and NQO-1; <italic>in vivo</italic> suppression of tumor growth and expression of Ki-67 and PCNA; more profound in combination with irradiation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B148" ref-type="bibr">Zhang et al., 2017</xref></td></tr><tr><td valign="top" rowspan="3" colspan="1"></td><td valign="top" rowspan="1" colspan="1">786-O, RCC4 clear-cell renal cell carcinoma (ccRCC);<break></break>786-O xenograft mouse model</td><td valign="top" rowspan="1" colspan="1">2.5, 5, 10 µM;<break></break>40, 80 mg/kg daily for 24 days</td><td valign="top" rowspan="1" colspan="1">Suppression of cell growth; induction of apoptosis; inhibition of cell invasion; increased miR-101 expression; repression of RLIP76 expression; inhibition of Akt <italic>in vivo</italic> suppression of tumor growth and pulmonary metastasis</td><td valign="top" rowspan="1" colspan="1"><xref rid="B138" ref-type="bibr">Wang et al., 2017a</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">HCT-116, SW480 colorectal cancer (CRC) cells;<break></break>HCT-116 xenograft mouse model</td><td valign="top" rowspan="1" colspan="1">5, 10 µM;<break></break>25, 50 mg/kg daily for 24 days i.p.</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation; induction of apoptosis; increased DNA double-strand breaks by inhibiting DNA repair <italic>via</italic> RAD51 downregulation; suppression of CRC tumor growth without adverse effects on normal tissues; downregulation of <italic>in situ</italic> levels of Ki-67, Bcl-2 and RAD51; increased cleaved caspase-3 and Bax in tumor tissues</td><td valign="top" rowspan="1" colspan="1"><xref rid="B70" ref-type="bibr">Li et al., 2019</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">PC-3 prostate cancer cells</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> > 30 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B91" ref-type="bibr">Nana et al., 2012</xref></td></tr><tr><td valign="top" rowspan="7" colspan="1">Anticancer activity</td><td valign="top" rowspan="1" colspan="1">A375, SK-MEL-1 melanoma cells;<break></break>B16-F10 mouse model of lung metastasis</td><td valign="top" rowspan="1" colspan="1">5, 10 µM;<break></break>20, 50 mg/kg daily for 24 days (intragastric route)</td><td valign="top" rowspan="1" colspan="1">Inhibition of cell proliferation; impaired metastatic potential by downregulating COX-2 via the miR-124/SPHK 1 axis; decreased number of lung metastases; decreased COX-2 and SPHK1 expression and increased miR-124 expression in metastatic tissues</td><td valign="top" rowspan="1" colspan="1"><xref rid="B41" ref-type="bibr">Gao et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">EC9706, KYSE30 ESCC cell lines;<break></break>KYSE30 xenograft mouse model</td><td valign="top" rowspan="1" colspan="1">10, 20 µM;<break></break>50, 100 mg/kg daily for 30 days</td><td valign="top" rowspan="1" colspan="1">Suppression of cell proliferation and tumor growth;<break></break>Induction of apoptosis by upregulating the miR-370/PIM1 signaling</td><td valign="top" rowspan="1" colspan="1"><xref rid="B44" ref-type="bibr">Han et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">CCRF-CEM, CEM/ADR5000 leukemia cells</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Strong inhibition of cell proliferation (degree of resistance = 0.62); induction of G0/G1 cell cycle arrest and apoptosis in CCRF-CEM cells through caspase 3/7 activation, mitochondrial membrane potential loss, and ROS production</td><td valign="top" rowspan="1" colspan="1"><xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">MDA-MB-231-pcDNA3, MDA-MB-231- BCRP clone 23 breast cancer cells</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Moderate inhibition of cell proliferation (degree of resistance = 1.54)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">HCT116 (<italic>p</italic>53<sup>+/+</sup>), HCT116 (<italic>p</italic>53<sup>−/−</sup>) colon cancer cells</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Moderate inhibition of cell proliferation (degree of resistance = 0.86)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">U87MG, U87MG.Δ<italic>EGFR</italic> glioblastoma cells</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">Moderate inhibition of cell proliferation (degree of resistance = 0.90)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">T47D, MDA-MB-231 breast cancer cells</td><td valign="top" rowspan="1" colspan="1">1, 3, 10 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of hypoxia-induced and iron chelator-induced HIF-1 activation in T47D cells; inhibition of MDA-MB-231 cell migration and chemotaxis</td><td valign="top" rowspan="1" colspan="1"><xref rid="B75" ref-type="bibr">Liu et al., 2009</xref></td></tr><tr><td valign="top" rowspan="5" colspan="1">Antidiabetic activity</td><td valign="top" rowspan="1" colspan="1">α-glucosidase</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 73.3 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of α-glucosidase activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B40" ref-type="bibr">Fu et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Protein tyrosine phosphatase-1B (PTP1B)</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 42.0 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of PTP1B activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B88" ref-type="bibr">Na et al., 2006</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">PTP1B</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 21.2 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of PTP1B activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B129" ref-type="bibr">Trinh et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">L6 myotubes; PTP1B</td><td valign="top" rowspan="1" colspan="1">1, 10, 25 µM</td><td valign="top" rowspan="1" colspan="1">Stimulation of basal and insulin-treated glucose-uptake in L6 myotubes by increasing AMPK activation, glucose transporters mRNA expression; moderate inhibition of PTP1B (IC<sub>50</sub> = 37.52 µM)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B66" ref-type="bibr">Lee et al., 2009b</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Acyl-CoA:diacylglycerol acyltransferase (DGAT)</td><td valign="top" rowspan="1" colspan="1">12.5 µg/ml</td><td valign="top" rowspan="1" colspan="1">Inhibition of DGAT activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B100" ref-type="bibr">Oh et al., 2009</xref></td></tr><tr><td valign="top" rowspan="2" colspan="1">Neuroprotective activity</td><td valign="top" rowspan="1" colspan="1">Monoamine oxidases (MAOs)</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 25.8, 52.6, 16.8 µM, respectively</td><td valign="top" rowspan="1" colspan="1">Inhibition of mixed mouse total brain MAO, MAO-A and MAO-B activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B43" ref-type="bibr">Han et al., 2005</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">SH-SY5Y neuroblastoma cells</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> > 25 µM</td><td valign="top" rowspan="1" colspan="1">Attenuation of 6-hydroxydopamine-induced neurotoxicity and ROS generation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B57" ref-type="bibr">Kim et al., 2017</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Antiplasmodial activity</td><td valign="top" rowspan="1" colspan="1"><italic>Plasmodium falciparum</italic></td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 1.98 µg/ml</td><td valign="top" rowspan="1" colspan="1">Inhibition of parasite proliferation</td><td valign="top" rowspan="1" colspan="1"><xref rid="B127" ref-type="bibr">Tjahjandarie and Tanjung, 2015b</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">Anti-HIV</td><td valign="top" rowspan="1" colspan="1">HIV-1 protease</td><td valign="top" rowspan="1" colspan="1">IC<sub>50</sub> = 30.1 µM</td><td valign="top" rowspan="1" colspan="1">Inhibition of HIV-1 protease activity</td><td valign="top" rowspan="1" colspan="1"><xref rid="B65" ref-type="bibr">Lee et al., 2009a</xref></td></tr></tbody></table><table-wrap-foot><p>Akt, protein kinase B; BV/TV ratio, bone volume/total volume ratio; cMyc, myelocytomatosis viral oncogene homolog; COX-2, cyclooxygenase-2; DPPH, l,l-diphenyl-2-picrylhydrazyl; ER, estrogen receptor; ERK, extracellular signal-regulated kinase; GREB1, growth regulation by estrogen in breast cancer 1; HIF-1, hypoxia-inducible factor-1; HO-1, heme oxygenase-1; ICAM-1, intercellular adhesion molecule-1; IZ, inhibition zone; JNK, c-Jun N-terminal kinases; LRH-1, liver receptor homologue 1; MAPKs, mitogen-activated protein kinases; MIC, minimum inhibitory concentration; NF-κB, nuclear factor-kappa B; NLRP3, nucleotide-binding domain-like receptor protein 3; NQO-1, NADPH:quinoneoxidoreductase-1; PARP; poly-ADP Ribose polymerase; PCNA; proliferating cell nuclear antigen; PIM1; Pim family kinases 1; RANKL; receptor activator of nuclear factor kappa-B ligand; ROS, reactive oxygen species; SPHK1, sphingosine kinase 1; Tb.N, trabecular number (linear bone density of the trabecular bone); Tb.Sp, trabecular separation (distance between the edges of the trabecular bone); Tb.Th, trabecular thickness.</p></table-wrap-foot></table-wrap><sec id="s2_1"><title>Estrogenic and Antiestrogenic Activities</title><p>Estrogenic plant-derived products act <italic>via</italic> binding to human estrogen receptors (ERs). AIF was found to be a weak ERα and ERβ binder with conflicting results concerning the preference for ERβ versus ERα (<xref rid="B33" ref-type="bibr">Djiogue et al., 2009</xref>; <xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref>; <xref rid="B85" ref-type="bibr">Mvondo et al., 2012</xref>). The authors used the same estrogen receptor competitor assay based on fluorescence polarization in the same laboratory and according to the instructions of the same manufacturer. The discrepancies can probably be ascribed to the purity of compound. The ER competitive ligand binding assay cannot distinguish between estrogenic and antiestrogenic substances and does not provide insight into the ability of a substance to initiate the molecular cascade leading to altered gene expression (<xref rid="B67" ref-type="bibr">Legler et al., 1999</xref>). To overcome this disadvantage, reporter gene assays such as the ER-mediated chemically activated luciferase gene expression assay (ER-CALUX) and the yeast estrogen screen (YES) based on stably transfected cell lines are usually applied. In an ER-CALUX assay using human osteosarcoma U2OS cells stably transfected with ERα and transiently transfected with ERβ, AIF stimulated the endogenous ER-estrogen response element (ERE) interaction and, thus, the luciferase reporter gene activity (<xref rid="B33" ref-type="bibr">Djiogue et al., 2009</xref>; <xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref>). However, in a yeast two-hybrid β-galactosidase assay, AIF failed to induce the ligand-dependent interaction of ERα and coactivator TIF2 as determined by the expression of a reporter gene, β-galactosidase (<xref rid="B102" ref-type="bibr">Okamoto et al., 2006</xref>). Although ER-CALUX and YES assays rely on the same principle and use the same receptors, the yeast cell wall is usually less permeable to compounds compared to mammalian cell membranes (<xref rid="B67" ref-type="bibr">Legler et al., 1999</xref>). This makes the ER-CALUX assay robust, more sensitive and more predictable than the YES assay (<xref rid="B69" ref-type="bibr">Leusch et al., 2010</xref>). In MCF-7 cells, AIF upregulated ERα target genes such as proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E1, cMyc (myelocytomatosis viral oncogene homologue), and liver receptor homologue 1 (LRH-1), and downregulated growth regulation by estrogen in breast cancer 1 (GREB1) (<xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref>). On the other hand, AIF suppressed estradiol (E2)-induced activity in U2OS-ERβ cells but not in U2OS-ERα cells and ERα yeast two-hybrid systems (<xref rid="B102" ref-type="bibr">Okamoto et al., 2006</xref>; <xref rid="B78" ref-type="bibr">Magne Nde et al., 2012</xref>). Antagonizing the ERβ-mediated signaling pathway in the presence or absence of E2 is not promising as ERβ is known to counteract the proliferative responses of ERα involved in estrogen-related cancers, osteoporosis, and cardiovascular diseases.</p><p>In <italic>in vivo</italic> studies AIF induced estrogen-like effects by increasing uterine wet weight as well as uterine and vaginal epithelial height in ovariectomized Wistar rats (<xref rid="B86" ref-type="bibr">Mvondo et al., 2011</xref>, <xref rid="B85" ref-type="bibr">Mvondo et al., 2012</xref>). In this model, AIF also reduced the hot flush index by increasing the FSH/LH ratio. It displayed atheroprotective effects by an augmentation of HDL-cholesterol levels, a reduction in the atherogenic index of plasma (<xref rid="B86" ref-type="bibr">Mvondo et al., 2011</xref>), and by upregulating the expression of estrogen-sensitive genes associated with bile acid formation (Cyp7a1) (<xref rid="B87" ref-type="bibr">Mvondo et al., 2015</xref>). Taken together, the <italic>in vitro</italic> and <italic>in vivo</italic> systems/models used to study estrogenic effects of AIF are quite suitable. The investigations demonstrated that AIF, through activation of ERs and modulation of estrogen-sensitive genes, exhibited estrogenic activities on uterus and vagina and by influencing several factors reduced the atherogenic risk. Nevertheless, further <italic>in vivo</italic> studies are necessary to get deeper insight into its potential.</p></sec><sec id="s2_2"><title>Antiosteoporotic Activity</title><p>Isoflavonoids are increasingly considered as a promising first-line prophylaxis for osteoporosis in clinical settings (<xref rid="B77" ref-type="bibr">Ma et al., 2008</xref>; <xref rid="B62" ref-type="bibr">Lambert and Jeppesen, 2018</xref>). The therapeutic strategies globally emphasize the inhibition of “osteoclast-mediated bone resorption” and/or the prevention of the apoptosis of osteoblasts and osteocytes.</p><p>Using experimental protocols of postmenopausal or glucocorticoid-induced osteoporosis, AIF exhibited an antiosteoporotic activity both <italic>in vitro</italic> and <italic>in vivo</italic>. A 6-week oral treatment with AIF (10 and 25 mg/kg) prevented ovariectomy-induced osteoporosis in mice by suppressing osteoclast differentiation (<xref rid="B28" ref-type="bibr">Cong et al., 2017</xref>). Despite its limits (<xref rid="B35" ref-type="bibr">Egermann et al., 2005</xref>; <xref rid="B68" ref-type="bibr">Lelovas et al., 2008</xref>), the ovariectomized rat/mouse model is the most widely used animal model in research on postmenopausal osteoporosis. Long-term exposure to glucocorticoids, e.g., in the treatment of chronic autoimmune and pulmonary disorders, cancers of the lymphoid system, as well as in the prevention of transplant rejection (<xref rid="B98" ref-type="bibr">Oakley and Cidlowski, 2013</xref>), is the primary cause of the secondary osteoporosis (<xref rid="B125" ref-type="bibr">Tanaka, 2014</xref>). In dexamethasone-induced osteoporosis in rats, 20 and 40 mg/kg AIF p.o. prevented bone loss (<xref rid="B139" ref-type="bibr">Wang et al., 2017b</xref>). <italic>In vitro</italic>, 5–20 µM AIF abrogated the dexamethasone-induced cytotoxicity and proapoptotic effects on osteoblasts and osteocytes (MC3T3-E1 and MLO-Y4 cells) through the inhibition of ROS production as well as through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and AMPK-dependent NAD(P)H oxidase 2 (Nox2) signaling pathways (<xref rid="B139" ref-type="bibr">Wang et al., 2017b</xref>; <xref rid="B147" ref-type="bibr">Yin et al., 2018</xref>). Osteoporosis remains an important target of research (<xref rid="B46" ref-type="bibr">Hendrickx et al., 2015</xref>), and, despite some limits, the two described animal models are appropriate and closer to the human situation than other models. Although further investigation is needed, the available studies showed that AIF, by suppressing osteoclast differentiation or osteoblasts and osteocytes apoptosis, could have beneficial effects on postmenopausal- and glucocorticoid-induced bone damage.</p></sec><sec id="s2_3"><title>Antioxidant and Anti-Inflammatory Activities</title><p>Through free radical-scavenging and antioxidative effects, antioxidants constitute the first line of defense against the pathogenesis of several diseases (<xref rid="B108" ref-type="bibr">Rani, 2017</xref>).</p><p>AIF showed radical scavenging activity against l,l-diphenyl-2-picrylhydrazyl (DPPH) radicals (<xref rid="B107" ref-type="bibr">Rahman et al., 2010</xref>; <xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>; <xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref>; <xref rid="B1" ref-type="bibr">Akter et al., 2016</xref>; <xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>). IC<sub>50</sub> values of 8.30 μg/ml (<xref rid="B107" ref-type="bibr">Rahman et al., 2010</xref>), 54.02 μg/ml (<xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>), 54.80 μM (<xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>), and 708.50 μM (<xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref>) were determined. In lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 and in mice with LPS-stimulated acute lung injury (ALI), 5 and 10 µg/ml AIF significantly increased the production of antioxidative enzymes such as catalase, heme oxygenase-1 (HO-1), glutathione peroxidase, and superoxide dismutase (<xref rid="B71" ref-type="bibr">Li et al., 2018</xref>).</p><p>There is a long and ever-growing list of <italic>in vitro</italic> antioxidant assays. In the DPPH free radical scavenging assay, quite different IC<sub>50</sub> values were obtained with AIF probably due to the differences in assay conditions (<xref rid="T3" ref-type="table"><bold>Table 3</bold></xref>). Variable DPPH concentrations, incubation times, sample volumes, solvent systems, and pH clearly result in large differences in IC<sub>50</sub> values (reviewed by <xref rid="B124" ref-type="bibr">Tan and Lim, 2015</xref>). To standardize the methodology and ensure comparability between studies or laboratories, a DPPH concentration of 50 µM (for good accuracy), an incubation time of 30 min, and methanol as solvent for less polar samples or buffered methanol for more polar samples have been proposed (<xref rid="B117" ref-type="bibr">Sharma and Bhat, 2009</xref>; <xref rid="B83" ref-type="bibr">Mishra et al., 2012</xref>). Results expressed in different units additionally impede cross-comparison in many cases. The DPPH assay does not actually measure the antioxidant activity but the reducing capacity of the sample (<xref rid="B8" ref-type="bibr">Benzie and Strain, 1999</xref>). Moreover, there is no linear relationship between the antioxidant concentration and the radical scavenging activity. The numerous drawbacks of this assay underline its ineptitude to evaluate the antioxidant capacity. Among the other single electron transfer (SET)-based assays such as the trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), and thiobarbituric acid reactive substances (TBARS), TEAC assay is most popular due to its convenient application which better reflects the antioxidant activity (<xref rid="B39" ref-type="bibr">Floegel et al., 2011</xref>). More recently, hydrogen atom transfer (HAT)-based assays like oxygen radical absorbance capacity (ORAC), total radical-trapping antioxidant parameter (TRAP), and crocin-bleaching assays provide better analogies to <italic>in vivo</italic> action (<xref rid="B106" ref-type="bibr">Prior et al., 2005</xref>). The main limits of TRAP (which relies only on the lag phase of the kinetic curve for quantitation) and the crocin-bleaching (easily disturbed by compounds absorbing at the monitored wavelength of 450 nm, crocin is not sold as pure compound but as an extract of saffron) assays are probably the reason why the ORAC assay is currently preferred in food and pharmaceutical industries (<xref rid="B51" ref-type="bibr">Huang et al., 2005</xref>; <xref rid="B19" ref-type="bibr">Číž et al., 2010</xref>; <xref rid="B105" ref-type="bibr">Power et al., 2013</xref>). According to <xref rid="B124" ref-type="bibr">Tan and Lim (2015)</xref>, a mix of SET and HAT-based assays, encompassing several different radical types is recommended to better estimate the overall antioxidant activity of a sample. In summary, the DPPH assay is not appropriate to evaluate the antioxidant activity of a sample. Moreover, the studies recorded in this review did not use the standardized protocols. However, results from the LPS-induced ALI protocol, well known to be associated with the production of ROS and oxidative stress (<xref rid="B122" ref-type="bibr">Su et al., 2014</xref>; <xref rid="B146" ref-type="bibr">Yeh et al., 2014</xref>), indicate that, <italic>via</italic> an activation of antioxidative enzymes, AIF could be beneficial in the treatment of diseases associated with oxidative stress.</p><table-wrap id="T3" position="float"><label>Table 3</label><caption><p>Assay conditions of the DDPH method in studies recorded in this review.</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" rowspan="1" colspan="1">Studies</th><th valign="top" rowspan="1" colspan="1">DPPH concentration</th><th valign="top" rowspan="1" colspan="1">Solvent for sample (pH)</th><th valign="top" rowspan="1" colspan="1">Sample volume</th><th valign="top" rowspan="1" colspan="1">Incubation time (min)</th><th valign="top" rowspan="1" colspan="1">Standard compound</th></tr></thead><tbody><tr><td valign="top" rowspan="1" colspan="1"><xref rid="B11" ref-type="bibr">Bórquez et al. (2013)</xref></td><td valign="top" rowspan="1" colspan="1">400 µM</td><td valign="top" rowspan="1" colspan="1">Methanol (–)</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">30</td><td valign="top" rowspan="1" colspan="1">Quercetin</td></tr><tr><td valign="top" rowspan="1" colspan="1"><xref rid="B40" ref-type="bibr">Fu et al. (2018)</xref></td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">Propyl gallate</td></tr><tr><td valign="top" rowspan="1" colspan="1"><xref rid="B107" ref-type="bibr">Rahman et al. (2010)</xref></td><td valign="top" rowspan="1" colspan="1">20 mg/l</td><td valign="top" rowspan="1" colspan="1">Methanol (–)</td><td valign="top" rowspan="1" colspan="1"></td><td valign="top" rowspan="1" colspan="1">20</td><td valign="top" rowspan="1" colspan="1"><italic>Tert</italic>-butyl-1-hydroxytoluene</td></tr><tr><td valign="top" rowspan="1" colspan="1"><xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung (2015a)</xref></td><td valign="top" rowspan="1" colspan="1">500 µM</td><td valign="top" rowspan="1" colspan="1">Methanol + 0.1 M buffer acetate (pH 5.5)</td><td valign="top" rowspan="1" colspan="1">–</td><td valign="top" rowspan="1" colspan="1">30</td><td valign="top" rowspan="1" colspan="1">Ascorbic acid</td></tr></tbody></table><table-wrap-foot><p>–, not indicated.</p></table-wrap-foot></table-wrap><p>The overproduction of free radicals is usually associated with excessive or sustained inflammatory reactions (<xref rid="B31" ref-type="bibr">Dandekar et al., 2015</xref>). Administered 1 h before LPS challenge, AIF (10 mg/kg i.p.) alleviated LPS-induced lung lesions, pulmonary edema, and hemorrhages by reducing the activity of myeloperoxidase (<xref rid="B71" ref-type="bibr">Li et al., 2018</xref>). In this model and in LPS-induced RAW264.7 cells, 5 and 10 µg/ml AIF inhibited the production of proinflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1b, intercellular adhesion molecule-1 (ICAM-1), and nitric oxide (NO). The mechanisms underlying these activities include the suppression of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome, and IL-17 signaling pathways (<xref rid="B71" ref-type="bibr">Li et al., 2018</xref>). A similar effect on LPS-induced NO production in RAW264.7 cells was observed by <xref rid="B89" ref-type="bibr">Namkoong et al. (2011)</xref> with an IC<sub>50</sub> value of 15.97 µM. In GOLD docking fitness, AIF displayed a fitness score of 35.42 against cyclooxygenase (COX)-2, an inducible enzyme only expressed after an inflammatory stimulus (<xref rid="B130" ref-type="bibr">Uddin et al., 2014</xref>). Four hours after administration, AIF (25 mg/kg i.p.) reduced the carrageenan-induced rat paw edema by 29% in male Wistar rats, whereas the positive control indomethacin (10 mg/kg i.p.) reduced it by 41.67% (<xref rid="B3" ref-type="bibr">Amen et al., 2013</xref>). The models used in studies recorded in this review including the carrageenan-induced rat paw edema and the LPS-induced ALI are well-established to study the anti-inflammatory potential of chemicals. Therefore, results from these models provide a strong evidence of the anti-inflammatory potential of AIF.</p></sec><sec id="s2_4"><title>Antimicrobial Activity</title><p>Over the last decade, the antimicrobial properties of AIF have been evaluated against several drug-resistant and drug-susceptible strains using agar disk diffusion (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>), broth microdilution (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>; <xref rid="B18" ref-type="bibr">Chukwujekwu et al., 2011</xref>; <xref rid="B137" ref-type="bibr">Wang et al., 2014</xref>; <xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>) and macrodilution assays (<xref rid="B113" ref-type="bibr">San-Martín et al., 2015</xref>), thin layer chromatography (TLC) bioautography (<xref rid="B1" ref-type="bibr">Akter et al., 2016</xref>), and computer-based (virtual) (<xref rid="B114" ref-type="bibr">Sathishkumar and Tharani, 2017</xref>) methods.</p><p>Tuberculosis (TB) is the leading human infectious-related cause of death (<xref rid="B142" ref-type="bibr">WHO, 2017</xref>). Usually, nonpathogenic mycobacterial species such as <italic>Mycobacterium smegmatis</italic> are used as model systems (<xref rid="B2" ref-type="bibr">Altaf et al., 2010</xref>; <xref rid="B90" ref-type="bibr">Namouchi et al., 2017</xref>). <italic>M. smegmatis</italic> displays an identical susceptibility to that of multidrug-resistant (MDR) clinical isolates of <italic>Mycobacterium tuberculosis</italic> for the two frontline anti-TB drugs isoniazid and rifampicin (<xref rid="B14" ref-type="bibr">Chaturvedi et al., 2007</xref>). AIF displayed a minimum inhibitory concentration (MIC) of 19.53 μg/ml and a minimum bactericidal concentration (MBC) of 39.06 μg/ml against <italic>M. smegmatis</italic> MC2 155 (32-fold less active than ciprofloxacin) while showing no activity against <italic>M. smegmatis</italic> ATCC14468 (<xref rid="B113" ref-type="bibr">San-Martín et al., 2015</xref>) and <italic>M. tuberculosis</italic> H37Rv (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>).</p><p>AIF also prevented the growth of Gram-negative (<italic>Enterobacter cloacae</italic>, <italic>Escherichia coli</italic>, <italic>Morganella morganii</italic>, and <italic>Proteus mirabilis</italic>) and Gram-positive (<italic>Staphylococcus aureus</italic> and <italic>Bacillus stearothermophilus</italic>) bacteria with inhibition zones (IZ) of 15.5–18.5 mm. Only the effects against <italic>E. coli</italic> (IZ = 7.0 mm) were weaker. MIC values of 39.06 μg/ml (against <italic>E. cloacae</italic>, <italic>M. morganii</italic>, <italic>S. aureus</italic>, and <italic>B. stearothermophilus</italic>) and an MBC of 78.12 μg/ml (only against <italic>M. morganii</italic>) were determined. In this series, AIF was less active than the reference gentamycin (IZ = 23.8–31.7 mm; MIC = 2.44–9.76 μg/ml) (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>). In a study by <xref rid="B18" ref-type="bibr">Chukwujekwu et al. (2011)</xref>, AIF displayed MICs of 3.9 μg/ml (against <italic>S. aureus</italic>, <italic>E. coli</italic>, and <italic>Klebsiella pneumoniae</italic>) and 7.8 μg/ml (against <italic>Bacillus subtilis</italic>), while those of the reference neomycin ranged between 0.78 and 1.6 μg/ml. Weak inhibitory activity (MIC ≥ 64 μg/ml) was observed against drug-resistant (SA1199B, RN4220, EMRSA-15, XU212, and EMRSA-16) and wild-type strains of <italic>S. aureus</italic> (<xref rid="B137" ref-type="bibr">Wang et al., 2014</xref>). Using a TLC bioautography assay, <xref rid="B1" ref-type="bibr">Akter et al. (2016)</xref> reported minimum inhibitory quantities of 15 μg for methicillin-sensitive <italic>S. aureus</italic> and 30 μg for a methicillin-resistant and an isolated multidrug resistant strain of <italic>S. aureus</italic>. By contrast, AIF did not show antibacterial activity against the clinical isolates of <italic>S. aureus</italic>, <italic>M. morganii</italic>, <italic>E. coli</italic>, and <italic>Klebsiella granulomatis</italic> in a study by <xref rid="B113" ref-type="bibr">San-Martín et al. (2015)</xref>. This might be explained by differences in the methods and microbial strains.</p><p><italic>Chlamydia trachomatis</italic> is the most common infectious cause of trachoma. By significantly interacting (G.score of –2.5 kcal/mol) with the active site residue GLU-626(O-H) of contact-dependent secretion D (CdsD) protein <italic>in silico</italic>, AIF might disrupt the assembly of the type III secretion system (T3SS) involved in differentiation, replication, and dissemination <italic>C. trachomatis</italic> (<xref rid="B114" ref-type="bibr">Sathishkumar and Tharani, 2017</xref>).</p><p>AIF was fungistatic against wild (MIC = 0.25 μg/ml) and ATCC18804 (MIC = 0.50 μg/ml) strains of <italic>Candida albicans</italic> (<xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>). At the concentration of 50 μg/ml, AIF was not able to inhibit the activity of fatty acid synthase (a potential antifungal target) and the growth of <italic>C. albicans</italic> ATCC90028 and <italic>Cryptococcus neoformans</italic> ATCC90113 (<xref rid="B73" ref-type="bibr">Li et al., 2002</xref>). It did not display any activity against <italic>Candida glabrata</italic> (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>).</p><p>The antibacterial activity of flavonoids is often widely conflicting mainly due to the use of different nonstandardized techniques. To overcome this issue, the Clinical and Laboratory Standards Institute (CLSI) and the European Committee for Antimicrobial susceptibility testing (EUCAST) have approved and published some guidelines over the last two decades (<xref rid="B23" ref-type="bibr">CLSI, 1998</xref>; <xref rid="B26" ref-type="bibr">CLSI, 2002</xref>; <xref rid="B20" ref-type="bibr">CLSI, 2004</xref>; <xref rid="B27" ref-type="bibr">CLSI, 2008</xref>; <xref rid="B21" ref-type="bibr">CLSI, 2010a</xref>; <xref rid="B22" ref-type="bibr">CLSI, 2010b</xref>; <xref rid="B25" ref-type="bibr">CLSI, 2012a</xref>; <xref rid="B24" ref-type="bibr">CLSI, 2012b</xref>; <xref rid="B37" ref-type="bibr">EUCAST Definitive Document, 2000</xref>; <xref rid="B38" ref-type="bibr">EUCAST Discussion Document, 2003</xref>). However, despite these guidelines for agar dilution, broth microdilution, and broth macrodilution, results from nonstandardized protocols are still published even in highly reputable journals. Although the disk diffusion technique is easy to apply without specialized equipment, and cheap, the determined IZ value is not related to the antibacterial activity but depends on polarity, concentration, and molecular weight of compounds (<xref rid="B124" ref-type="bibr">Tan and Lim, 2015</xref>). Thus, highly polar compounds display a high IZ, and many compounds with the same diffusion rate result in quite different antimicrobial activities. This method is only useful for a simple qualitative screening. It does not allow the quantification of the amount of the antimicrobial agent diffused into the agar, impeding the determination of MICs and MBCs (<xref rid="B93" ref-type="bibr">Ncube et al., 2008</xref>; <xref rid="B6" ref-type="bibr">Balouiri et al., 2016</xref>). The broth macrodilution or microdilution assays are among the most appropriate methods to determine MIC and MBC values despite the fact that they are unsuitable for highly nonpolar compounds (<xref rid="B124" ref-type="bibr">Tan and Lim, 2015</xref>). The reproducibility and the low price due to small amounts of reagents are the main advantages of the microdilution assay over the macrodilution assay. The latter is tedious to perform, requires a lot of manual handling, and is associated with a risk of errors in the preparation of antimicrobial solutions (<xref rid="B54" ref-type="bibr">Jorgensen and Ferraro, 2009</xref>). Accordingly, the microdilution method appears to be more accurate. In general, the interpretation of the efficacy depends on the profound knowledge of the model and the used protocol. Nevertheless, stringent endpoint criteria have been set to MIC values of <10 µg/ml or <25 µM for promising plant compounds (<xref rid="B111" ref-type="bibr">Ríos and Recio, 2005</xref>; <xref rid="B29" ref-type="bibr">Cos et al., 2006</xref>). According to this criterion, AIF could be considered promising only against <italic>S. aureus</italic> ATCC12600, <italic>E. coli</italic> ATCC11775, <italic>K. pneumonia</italic> ATCC13883, <italic>B. subtilis</italic> ATCC6051, and wild and ATCC18804 strains of <italic>C. albicans</italic>. Overall, despite the limits of the used assays/protocols and the discrepancies in results, recorded data suggest the potential of AIF to act as an antimicrobial drug against few microorganisms.</p></sec><sec id="s2_5"><title>Anticancer Activity</title><p>Different studies reported promising anticancer activities of plant-derived (iso)flavonoids (<xref rid="B79" ref-type="bibr">Magne Nde et al., 2015</xref>; <xref rid="B96" ref-type="bibr">Nwodo et al., 2016</xref>; <xref rid="B103" ref-type="bibr">Patil and Masand, 2019</xref>) including the suppression of proliferation, migration/invasion, tumor angiogenesis and metastasis, and the promotion of apoptosis in various cancers.</p><p>In several studies the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to determine the cytotoxic effects of AIF: The compound exhibited strong cytotoxicity against human oral epidermoid carcinoma KB cells (IC<sub>50</sub> = 4.13 μg/ml) (<xref rid="B95" ref-type="bibr">Nkengfack et al., 2001</xref>) and murine leukemia P-388 (IC<sub>50</sub> = 4.31 μg/ml) cells (<xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjung, 2015a</xref>). IC<sub>50</sub> values of 19, 34, and 41 μM, respectively, were observed against human leukemia HL-60, K-562, and MOLT-4 cell lines (<xref rid="B61" ref-type="bibr">Kumar et al., 2013</xref>). In human lung H2108, H1299, and MRC-5 cancer cell lines, AIF displayed moderate cytotoxicity with IC<sub>50</sub> values of 33.5, 38.8, and 52.5 µM, respectively (<xref rid="B89" ref-type="bibr">Namkoong et al., 2011</xref>). At the concentration of 10 µM, the growth and invasion of the human clear-cell renal carcinoma ccRCC 786-O and Caki1 cells were suppressed by 40 and 50–60%, respectively (<xref rid="B138" ref-type="bibr">Wang et al., 2017a</xref>). An IC<sub>50</sub> value of >25 μM was obtained against human prostate PC-3 (<xref rid="B91" ref-type="bibr">Nana et al., 2012</xref>) and neuroblastoma SH-SY5Y (<xref rid="B49" ref-type="bibr">Hong et al., 2018</xref>) cancer cells. At the concentration of 10<sup>−5</sup> M, AIF inhibited the growth of the renal SN12C cancer cells by 32.67% (<xref rid="B3" ref-type="bibr">Amen et al., 2013</xref>). AIF (10 μg/ml) displayed a low antiproliferative activity (30–40% inhibition) against the human melanoma A375 and SK-MEL-1 cells after a 24-h incubation and suppressed the migration and invasion of these cell lines (<xref rid="B41" ref-type="bibr">Gao et al., 2017</xref>). However, after 48 h of incubation, AIF did not exhibit inhibitory effects against SK-MEL-28 cells in a study by <xref rid="B50" ref-type="bibr">Hu et al. (2017)</xref>. The degree of cytotoxicity in MTT assay increases with the cell number, the concentration of MTT, and the incubation time (<xref rid="B132" ref-type="bibr">van Tonder et al., 2015</xref>). The concentration of MTT was not indicated in the two latter studies, and the cell number (5 × 10<sup>3</sup> cells/well) was only indicated by <xref rid="B50" ref-type="bibr">Hu et al. (2017)</xref>. Comparison of the incubation times showed that the higher incubation time (<xref rid="B50" ref-type="bibr">Hu et al., 2017</xref>) was associated with lower antiproliferative activity. Although neglected in the vast majority of studies, long incubation times are often associated with the decomposition, metabolism, or precipitation of compounds (<xref rid="B4" ref-type="bibr">Ateba et al., 2018</xref>).</p><p>Under use of a cell counting kit-8 (CCK-8) assay, AIF exhibited a moderate antiproliferative activity against human esophageal squamous carcinoma (ESCC) Eca109 and KYSE30 cells and at 5 µM enhanced the sensitivity of these cell lines to irradiation (<xref rid="B148" ref-type="bibr">Zhang et al., 2017</xref>). In the same model, it also reduced the viability of colorectal HCT-116 and SW480 cancer cells (IC<sub>50</sub> of 10 and 5 µM, respectively) (<xref rid="B70" ref-type="bibr">Li et al., 2019</xref>). The enzyme-based methods including CCK-8 and MTT assays are easy to use, safe, and have a high reproducibility. However, the toxicity of MTT as well as interference of polyphenols with the tetrazolium MTT dye has to be taken into consideration (<xref rid="B141" ref-type="bibr">Wang et al., 2010</xref>). A further advantage of the CCK-8 method is its far higher sensitivity (<uri xlink:type="simple" xlink:href="https://www.dojindo.eu.com/Shared/Flyers/Flyer_CCK-8-Rev.pdf">https://www.dojindo.eu.com/Shared/Flyers/Flyer_CCK-8-Rev.pdf</uri>)</p><p>At 10<sup>−5</sup> M, AIF inhibited the growth of leukemia CCRF-CEM, MOLT-4, and HL-60 cancer cells by 51.17, 26.15, and 15.49%, respectively. In this study, the type of assay was not specified (<xref rid="B3" ref-type="bibr">Amen et al., 2013</xref>).</p><p>Induction of apoptosis is a very important property of anticancer drug candidates. In 786-O and Caki1 cells, AIF led to apoptosis by modulating the miR-101/RLIP76 signaling pathway through the inhibition of Akt (<xref rid="B138" ref-type="bibr">Wang et al., 2017a</xref>). In addition to the induction of DNA damage and cell cycle arrest (<xref rid="B148" ref-type="bibr">Zhang et al., 2017</xref>), AIF induced apoptosis in ESCC cells by upregulating the miR-370/Pim family kinases 1 (PIM1) signaling (<xref rid="B44" ref-type="bibr">Han et al., 2016</xref>) and by suppressing the expression of Nrf2, HO-1 and NADPH:quinine oxidoreductase-1 (<xref rid="B148" ref-type="bibr">Zhang et al., 2017</xref>). In HL-60 leukemia cells, apoptotic cell death was observed <italic>via</italic> the suppression of NF-κB and the signal transducer and activator of transcription (STAT) signaling pathway (<xref rid="B61" ref-type="bibr">Kumar et al., 2013</xref>). AIF induced lung tumor apoptotic cell death by repressing both the ERK/MAPK and NF-κB pathways (<xref rid="B89" ref-type="bibr">Namkoong et al., 2011</xref>). In HCT-116 and SW480 cells, it triggered apoptosis by blocking DNA damage repair mediated by the DNA double-strand break repair gene RAD51 (<xref rid="B70" ref-type="bibr">Li et al., 2019</xref>) and in CCRF-CEM cells through the loss of MMP and production of ROS (<xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref>).</p><p>Drug resistance constitutes a major impediment to effective cancer treatment. AIF displayed antiproliferative effects against several MDR cancer cell lines. Strong antiproliferative activities were obtained for both the drug-sensitive CCRF-CEM (IC<sub>50</sub> = 9.6 μM) and the multidrug-resistant P-glycoprotein-overexpressing subline CEM/ADR5000 (IC<sub>50</sub> = 5.91 μM) cells (<xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref>). In other drug-sensitive cell lines [breast MDA-MB-231-pcDNA3, colon HCT116 (p53<sup>+/+</sup>), glioblastoma U87MG] and their MDR counterparts [MDA-MB-231-<italic>BCRP</italic> clone 23, HCT116 (p53<sup>−/−</sup>) and U87MG.<italic>ΔEGFR</italic>], AIF displayed moderate effects with IC<sub>50</sub> values of 42.4–46.7 and 36.4–65.6 μM, respectively. In comparison to normal AML12 hepatocytes, a selective index >3.13 was observed towards HepG2 liver cancer cells (<xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref>).</p><p>The role of increased activity of hypoxia-inducible factor-1 (HIF-1), especially HIF-1α is well known in cancer progression (<xref rid="B81" ref-type="bibr">Massoud and Li, 2015</xref>; <xref rid="B115" ref-type="bibr">Schito and Semenza, 2016</xref>). Hypoxic cancer cells seem to be resistant to radiation and chemotherapy (<xref rid="B112" ref-type="bibr">Rohwer and Cramer, 2011</xref>; <xref rid="B149" ref-type="bibr">Zhang et al., 2015</xref>). Therefore, targeting HIF-1 is an important approach for cancer prevention and treatment. AIF suppressed both hypoxia-induced and iron chelator-induced HIF-1 activation in T47D human breast cancer cells as well as MDA-MB-231 cell migration (<xref rid="B75" ref-type="bibr">Liu et al., 2009</xref>).</p><p>The antiproliferative or cytotoxic activity associated with apoptosis in malignant cells is a highly important target in the screening of anticancer drugs. Given the severe adverse reactions in normal tissues by tumoricidal doses of chemotherapeutic agents, the cytotoxic activity of drug candidates should also be evaluated against normal cells. In addition to a strong antiproliferative activity (IC<sub>50</sub> <4 µg/ml or <10 µM for a pure compound after 48–72 h incubation) (<xref rid="B10" ref-type="bibr">Boik, 2001</xref>), a high selectivity (selectivity index ≥3) towards malignant cells is needed. The inclusion of positive controls in respective studies of natural compounds is indispensable in good experimental practice (<xref rid="B4" ref-type="bibr">Ateba et al., 2018</xref>). Among the 13 <italic>in vitro</italic> studies recorded in this review, only one investigated the effects against normal cells (<xref rid="B61" ref-type="bibr">Kumar et al., 2013</xref>) and four used a positive control (<xref rid="B91" ref-type="bibr">Nana et al., 2012</xref>; <xref rid="B126" ref-type="bibr">Tjahjandarie and Tanjng, 2015a</xref>; <xref rid="B50" ref-type="bibr">Hu et al., 2017</xref>; <xref rid="B49" ref-type="bibr">Hong et al., 2018</xref>). In addition to this deficit, human tumor cell lines as the workhorse of cancer research are cultured since decades and do not adequately mirror (different tumor environment) the biology of human tumors (<xref rid="B7" ref-type="bibr">Ben-David et al., 2017</xref>). Therefore, <italic>in vivo</italic> models with better and more clinically predictive power of human cancers are an imperative.</p><p><italic>In vivo</italic>, AIF has been tested in various xenograft mouse models. After 30 consecutive days of treatment, the compound reduced tumor growth in KYSE30 (50 and 100 mg/kg/day) and Eca109 (20 mg/kg/day) xenograft mouse models (<xref rid="B44" ref-type="bibr">Han et al., 2016</xref>; <xref rid="B148" ref-type="bibr">Zhang et al., 2017</xref>). It also suppressed the tumor growth in an HCT-116 xenograft mouse model after 24 days treatment (25 and 50 mg/kg/day AIF i.p.) (<xref rid="B70" ref-type="bibr">Li et al., 2019</xref>). In a B16-F10 mouse lung model of metastasis, 24-day intragastrical administration of 20 and 50 mg/kg/day AIF decreased the number of metastatic pulmonary nodules. The reduction in COX-2 through modulating miR-124/SPHK1 axis was the underlying mechanism involved (<xref rid="B41" ref-type="bibr">Gao et al., 2017</xref>). The dose of 40 and 80 mg/kg/day for 24 days suppressed the growth and pulmonary metastatic nodules in a 786-O xenograft mouse model by modulating miR-101/RLIP76 signaling (<xref rid="B138" ref-type="bibr">Wang et al., 2017a</xref>). In a study by <xref rid="B148" ref-type="bibr">Zhang et al. (2017)</xref>, combination of AIF (20 mg/kg/day for 30 days) with irradiation induced a more profound tumor regression than single treatments. All these <italic>in vivo</italic> activities occurred without affecting the body weight of the mice. Despite the drawbacks of the majority of the current cell-line-derived or patient-derived mouse xenograft models reviewed by <xref rid="B63" ref-type="bibr">Landgraf et al. (2018)</xref>, they have become a prominent cancer model system over decades. For research in pharmaceutical industry, the accurate description of materials and methodology is indispensable to assure that experiments can be accurately replicated. However, the route of administration of AIF, an extremely important parameter, is not mentioned in the studies by <xref rid="B148" ref-type="bibr">Zhang et al. (2017)</xref> and <xref rid="B138" ref-type="bibr">Wang et al. (2017a)</xref>, published in “high-impact” journals. As a different route of administration leads to different results, this underlines the importance of an accurate review of such papers. Nevertheless, all data reported in this section demonstrate that AIF could have a potential to suppress some tumor growth <italic>in vivo</italic>.</p></sec><sec id="s2_6"><title>Antidiabetic Activity</title><p>Adequate glycemic control remains the main foundation of managing diabetes mellitus (DM) (<xref rid="B15" ref-type="bibr">Chaudhury et al., 2017</xref>). Retarding the release of D-glucose from dietary carbohydrates and delaying its absorption through the inhibition of α-glucosidase is an attractive therapeutic target for the treatment of DM, obesity, and other related complications (<xref rid="B131" ref-type="bibr">van de Laar et al., 2005</xref>). <italic>In vitro</italic>, AIF exhibited a moderate α-glucosidase inhibitory activity with an IC<sub>50</sub>value of 73.3 ± 12.9 μM (<xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>).</p><p>Protein tyrosine phosphatase 1B (PTP1B) is a negative key regulator of insulin signaling pathways that leads to insulin resistance. Thus, it is a promising molecular-level therapeutic target in the management of type 2 DM and obesity (<xref rid="B136" ref-type="bibr">Wang et al., 2015</xref>). In a study by <xref rid="B88" ref-type="bibr">Na et al. (2006)</xref>, AIF exhibited <italic>in vitro</italic> PTP1B inhibitory activity with an IC<sub>50</sub> value of 42 μM as compared to the positive controls RK-682 (IC<sub>50</sub> = 4.5 ± 0.5 μM) and ursolic acid (IC<sub>50</sub> = 3.6 ± 0.2 μM) (<xref rid="B129" ref-type="bibr">Trinh et al., 2017</xref>). By increasing the AMPK activation and the expression of glucose transporters’ (GLUT-4 and -1) mRNA as well as by inhibiting the PTP1B activity (IC<sub>50</sub> = 37.52 µM vs. ursolic acid—5.13 µM), AIF significantly stimulated the glucose uptake in L6 myotubes (<xref rid="B66" ref-type="bibr">Lee et al., 2009b</xref>). These differences in IC<sub>50</sub> values can be explained by the application of different experimental conditions. Using a nonkinetic method to estimate the amount of produced <italic>p</italic>-nitrophenol at 405 nm, <xref rid="B88" ref-type="bibr">Na et al. (2006)</xref> added 10 M NaOH to stop the reaction, while in the study of <xref rid="B129" ref-type="bibr">Trinh et al. (2017)</xref>, the release rate of <italic>p</italic>-nitrophenol (kinetic method) was determined by measuring the absorbance at 405 nm every 30 s for 10 min. Moreover, these studies used different concentrations of PTP1B and the substrate <italic>p</italic>-nitrophenyl phosphate.</p><p>Acyl-CoA:diacylglycerol acyltransferase (DGAT) is a key enzyme in the synthesis of triglycerides, the imbalance of which usually leads to insulin resistance and type 2 DM. At the concentration of 12.5 μg/ml, AIF induced 23% inhibition of the activity of this enzyme, while the positive control displayed an IC<sub>50</sub> value of 4.8 µg/ml (<xref rid="B100" ref-type="bibr">Oh et al., 2009</xref>).</p><p>Overall, these preliminary results suggest that AIF could exhibit a potential for the treatment of type 2 DM by retarding the glucose absorption from small intestine, by increasing the insulin sensitivity and the glucose transport into cells, and by improving triglycerides’ profile. But most important, this hypothesis has to be confirmed by respective meaningful <italic>in vivo</italic> models.</p></sec><sec id="s2_7"><title>Neuroprotective Activity</title><p>Elevation of the activity of brain monoamine oxidases (MAOs), especially MAO-B, contributes to chronic neurodegeneration and brain atrophy (<xref rid="B92" ref-type="bibr">Naoi et al., 2018</xref>; <xref rid="B128" ref-type="bibr">Tong et al., 2017</xref>). AIF inhibited the mixed type of mouse total brain MAO with an IC<sub>50</sub> value of 25.8 μM. Its activity on MAO-B (IC<sub>50</sub> = 16.8 μM) was 3.1-fold higher than that on MAO-A (<xref rid="B43" ref-type="bibr">Han et al., 2005</xref>). Globally, AIF was more active than the positive control amitriptyline on mixed MAO, MAO-A, and MAO-B. By destroying dopaminergic and noradrenergic neurons in the brain through excessive production of ROS such as superoxide radicals, the neurotoxin 6-hydroxydopamine (6-OHDA) induces neuronal cell death and Parkinson’s disease in rats (<xref rid="B45" ref-type="bibr">Heikkila et al., 1989</xref>; <xref rid="B104" ref-type="bibr">Perese et al., 1989</xref>; <xref rid="B116" ref-type="bibr">Schober, 2004</xref>). At noncytotoxic concentrations, AIF attenuated (IC<sub>50</sub> > 25 μM) the 6-OHDA-induced neurotoxicity and ROS generation in SH-SY5Y cells (<xref rid="B57" ref-type="bibr">Kim et al., 2017</xref>).</p><p>The relatively high MAO inhibitory activity of AIF compared to amitriptyline and its capacity to protect against 6-OHDA-induced neurotoxicity justifies further in-depth investigations of AIF for its potential in neurodegenerative diseases such as Parkinson’s and Alzheimer’s.</p></sec><sec id="s2_8"><title>Other Activities</title><p>With 216 million cases and 445,000 deaths in 2016, malaria remains a major cause of death worldwide, especially in Africa (<uri xlink:type="simple" xlink:href="http://www.who.int/malaria/en/">http://www.who.int/malaria/en/</uri>). AIF has shown strong antiplasmodial properties against <italic>Plasmodium falciparum</italic> with an IC<sub>50</sub> value of 1.98 µg/ml as compared with the positive control chloroquine (IC<sub>50</sub> = 1.02 µg/ml) (<xref rid="B127" ref-type="bibr">Tjahjandarie and Tanjung, 2015b</xref>).</p><p>HIV-1 protease and reverse transcriptase are the most important targets in the search for anti-HIV agents. <italic>In vitro</italic>, AIF showed a low inhibitory activity against HIV-1 protease with an IC<sub>50</sub> value of 30.1 μM (<xref rid="B65" ref-type="bibr">Lee et al., 2009a</xref>).</p></sec></sec><sec id="s3"><title>Structure-Activity Relationship</title><p>Numerous prenyl- (<xref rid="B50" ref-type="bibr">Hu et al., 2017</xref>), O-methyl- (<xref rid="B134" ref-type="bibr">Waffo et al., 2000</xref>; <xref rid="B43" ref-type="bibr">Han et al., 2005</xref>; <xref rid="B75" ref-type="bibr">Liu et al., 2009</xref>; <xref rid="B74" ref-type="bibr">Lim et al., 2012</xref>; <xref rid="B94" ref-type="bibr">Ndemangou et al., 2013</xref>; <xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>; <xref rid="B99" ref-type="bibr">Ocloo et al., 2017</xref>; <xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>), and/or O-acetyl (<xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>; <xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>) derivatives of AIF have been detected in various plants and studied for the impact on the biological activities. From studies comparing both the activities of AIF and those of one or more of its derivatives (<xref rid="T4" ref-type="table"><bold>Table 4</bold></xref>), it can be deduced that:</p><list list-type="roman-lower"><list-item><p>The replacement of C4′-OH and/or C5-OH by −OMe or O-acetyl reduces the antifungal activity against <italic>C. albicans</italic> (<xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>).</p></list-item><list-item><p>The 4′-O-methylated form of AIF promoted the inhibition of HIF-1 activation in T47D cells, the MDA-MB-231 cell migration (<xref rid="B75" ref-type="bibr">Liu et al., 2009</xref>), and the inhibition of urease (<xref rid="B94" ref-type="bibr">Ndemangou et al., 2013</xref>) and MAO-A (<xref rid="B43" ref-type="bibr">Han et al., 2005</xref>) activities, while no significant changes on the influence on MAO-B and α-glucosidase activities were observed (<xref rid="B43" ref-type="bibr">Han et al., 2005</xref>; <xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>).</p></list-item><list-item><p>In AIF, initially inactive, the introduction of a prenyl group at the C-8 position to obtain scandenolone or warangalone significantly increased the growth inhibitory activity (IC<sub>50</sub> < 5 μM) towards human melanoma SK-MEL-28 cells (<xref rid="B50" ref-type="bibr">Hu et al., 2017</xref>).</p></list-item><list-item><p>The [1, 2- <italic>b</italic>:5, 4- <italic>b</italic>’] dipyran derivative derrone showed antiproliferative activity in human leukemia U937 cells in a similar magnitude like AIF (<xref rid="B82" ref-type="bibr">Matsuda et al., 2007</xref>). The same refers to the inhibition of PTP1 (IC<sub>50</sub> = 12.6 µM for derrone and 21.6 µM for alpinumisoflavone) (<xref rid="B129" ref-type="bibr">Trinh et al., 2017</xref>). In contrast, derrone was moderately inhibiting phospholipase Cγ1 activity and the formation of inositol phosphates in phospholipase Cγ1-overexpressing NIH3T3 fibroblasts, whereas AIF remained without effect (<xref rid="B101" ref-type="bibr">Oh et al., 2005</xref>).</p></list-item></list><table-wrap id="T4" position="float"><label>Table 4</label><caption><p>Impact of different substitutions on the activity of alpinumisoflavone.</p></caption><table frame="hsides" rules="groups"><thead><tr><th valign="top" rowspan="1" colspan="1">Substituent</th><th valign="top" rowspan="1" colspan="1">Impact on the activity</th><th valign="top" rowspan="1" colspan="1">Experimental model</th><th valign="top" rowspan="1" colspan="1">References</th></tr></thead><tbody><tr><td valign="top" rowspan="7" colspan="1"><bold>4′-O-methyl</bold></td><td valign="top" rowspan="1" colspan="1">↑ Inhibition of hypoxia-inducible factor-1 (HIF-1) activation</td><td valign="top" rowspan="1" colspan="1">Human breast tumor T47D cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B75" ref-type="bibr">Liu et al., 2009</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↑ Inhibition of tumor cell migration and chemotaxis</td><td valign="top" rowspan="1" colspan="1">MDA-MB-231 cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B75" ref-type="bibr">Liu et al., 2009</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↓ Antiradical activity</td><td valign="top" rowspan="1" colspan="1">DPPH assay</td><td valign="top" rowspan="1" colspan="1"><xref rid="B40" ref-type="bibr">Fu et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↔Inhibition of α-glucosidase activity</td><td valign="top" rowspan="1" colspan="1">α-Glucosidase enzyme model</td><td valign="top" rowspan="1" colspan="1"><xref rid="B40" ref-type="bibr">Fu et al., 2018</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↓ Antifungal activity</td><td valign="top" rowspan="1" colspan="1"><italic>Candida albicans</italic> (wild and ATCC18804 strains)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↑ Monoamine oxidase-A (MAO-A) activity<break></break>↔ MAO-B activity</td><td valign="top" rowspan="1" colspan="1">Mitochondrial fraction from mouse brain</td><td valign="top" rowspan="1" colspan="1"><xref rid="B43" ref-type="bibr">Han et al., 2005</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1">↑ Inhibition of urease activity</td><td valign="top" rowspan="1" colspan="1"><italic>Helicobacter pylori</italic> urease enzyme assay</td><td valign="top" rowspan="1" colspan="1"><xref rid="B94" ref-type="bibr">Ndemangou et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>O,O-dimethyl</bold></td><td valign="top" rowspan="1" colspan="1">↓ Antifungal activity</td><td valign="top" rowspan="1" colspan="1"><italic>Candida albicans</italic> (wild and ATCC18804 strains)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>5-O-acetyl- and 4′-O-methyl</bold></td><td valign="top" rowspan="1" colspan="1">↓ Antifungal activity</td><td valign="top" rowspan="1" colspan="1"><italic>Candida albicans</italic> (wild and ATCC18804 strains)</td><td valign="top" rowspan="1" colspan="1"><xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>4´-O-acetyl</bold></td><td valign="top" rowspan="1" colspan="1">↓ Antiradical activity</td><td valign="top" rowspan="1" colspan="1">DPPH assay</td><td valign="top" rowspan="1" colspan="1"><xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref></td></tr><tr><td valign="top" rowspan="1" colspan="1"><bold>8-prenyl</bold></td><td valign="top" rowspan="1" colspan="1">↑ Antiproliferative activity</td><td valign="top" rowspan="1" colspan="1">Human melanoma SK-MEL-28 cells</td><td valign="top" rowspan="1" colspan="1"><xref rid="B50" ref-type="bibr">Hu et al., 2017</xref></td></tr></tbody></table><table-wrap-foot><p>↑; increase, ↓; decrease, ↔; not different.</p></table-wrap-foot></table-wrap><p>The differences in the activities of some compounds closely related to AIF, preclinically tested in comparable assays but not directly compared with AIF, are difficult to interpret due to the limitations as discussed above. Nevertheless, we include those results, which were obtained in the most similar experimental setups:</p><list list-type="roman-lower"><list-item><p>The 2′-OH derivative parvisoflavone B showed a stronger α-glucosidase inhibition (IC<sub>50</sub> = 12.2 µM; <xref rid="B32" ref-type="bibr">Dendup et al., 2014</xref>) than AIF (IC<sub>50</sub> = 73.3 µM; <xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>). Nevertheless, due to the lack of a positive control in the study with AIF, a comparison of the results remains questionable. Parvisoflavone B resulted also in a better cytotoxic effect against MDA-MB-231 breast cancer cells (EC<sub>50</sub> = 16.9 µM) (<xref rid="B97" ref-type="bibr">Nyandoro et al., 2017</xref>). The weak antimycobacterial effect (MIC = 90.9 µM) of parvisoflavone B against <italic>M. tuberculosis</italic> H37rV) (<xref rid="B97" ref-type="bibr">Nyandoro et al., 2017</xref>) differed from the inactive AIF (<xref rid="B59" ref-type="bibr">Kuete et al., 2008</xref>).</p></list-item><list-item><p>Cudraisoflavon M—carrying an additional 2,3-dihydroxy-prenyl group at C-8 of AIF—did not show any activity against 6-OHDA-induced cell death in SH-SY5Y cells (<xref rid="B48" ref-type="bibr">Hiep et al., 2017</xref>), whereas cudraisoflavon H with a prenyl group at C-8 and an additional hydroxy group at C-2″ of AIF resulted in an IC<sub>50</sub> value of 4.5 µM (<xref rid="B47" ref-type="bibr">Hiep et al., 2015</xref>).</p></list-item><list-item><p>The comparison of the antimicrobial effects of derrone with AIF is extremely difficult due to the differences in the experimental setup as discussed above. Nevertheless, the activity of derrone against <italic>E. coli</italic>, <italic>S. aureus</italic>, and <italic>C. albicans</italic> seems lower than the one of AIF (<xref rid="B36" ref-type="bibr">Edziri et al., 2012</xref>). The antiproliferative potential of derrone and AIF differ in dependence of the cell line: In SW480 cells, AIF with an IC<sub>50</sub> value of 5 µM inhibits the proliferation (<xref rid="B70" ref-type="bibr">Li et al., 2019</xref>), whereas derrone remains inactive (<xref rid="B72" ref-type="bibr">Li et al., 2017</xref>). In MCF-7 cells, AIF was inactive (<xref rid="B123" ref-type="bibr">Sudanich et al., 2017</xref>) and derrone at 10 µM inhibited this cell line by 13.6% (<xref rid="B72" ref-type="bibr">Li et al., 2017</xref>). HepG2 cells seem to be similarly sensitive to the two compounds [AIF—IC<sub>50</sub> 37.99 µM (<xref rid="B58" ref-type="bibr">Kuete et al., 2016</xref>); derrone—23.7% inhibition at 10 µM (<xref rid="B72" ref-type="bibr">Li et al., 2017</xref>)].</p></list-item><list-item><p>2′-Hydroxyerythrin A with the OH group from C-5 shifted to C-2′ showed good activity against several Gram-positive and Gram-negative bacteria (<xref rid="B140" ref-type="bibr">Wang et al., 2018</xref>). The magnitude of the DPPH radical scavenging effect was in the same range (<xref rid="B140" ref-type="bibr">Wang et al., 2018</xref>) as in some studies with AIF (<xref rid="B107" ref-type="bibr">Rahman et al., 2010</xref>; <xref rid="B11" ref-type="bibr">Bórquez et al., 2013</xref>; <xref rid="B40" ref-type="bibr">Fu et al., 2018</xref>).</p></list-item></list><p>The infrequence of studies and the low number of different substitution patterns and of investigated activities are the main drawback in the deduction of structure–activity relationships (SAR) of AIF and its derivatives. Continued efforts are needed to further synthesize or isolate new derivatives of AIF to expand SAR. Nevertheless, published data indicate that the C4′-O-methylation and the C8-prenylation increase the activity of AIF in cancer and neurodegenerative conditions. This is in accordance with <xref rid="B9" ref-type="bibr">Bernini et al. (2011)</xref> who indicated that O-methylation of flavonoids ensures a superior anticancer activity as compared with the corresponding hydroxylated derivatives, since such compounds are more resistant to hepatic metabolism and show higher intestinal absorption. In addition, <xref rid="B135" ref-type="bibr">Walle et al. (2007)</xref> suggested that O-methylation enhances the stability of flavonoids to metabolic degradation and increases their bioavailability as well as a higher tissue distribution as compared to unmethylated forms.</p></sec><sec id="s4"><title>Point of View and Future Perspective</title><p>Prenylated (iso)flavonoids are attracting more and more attention due to a series of promising biological activities ascribed to their increased lipophilicity and a strong affinity to biological membranes as compared to the respective unprenylated compounds (<xref rid="B13" ref-type="bibr">Botta et al., 2005</xref>; <xref rid="B12" ref-type="bibr">Botta et al., 2009</xref>; <xref rid="B17" ref-type="bibr">Chen et al., 2014</xref>; <xref rid="B119" ref-type="bibr">Sherif et al., 2015</xref>; <xref rid="B84" ref-type="bibr">Mukai, 2018</xref>). In this context, numerous pharmacological investigations of alpinumisoflavone, extracted from various medicinal plants, were carried out over the last decades. Data recorded in this review evidence a wide array of activities such as antiosteoporotic, antioxidant, anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective. Discrepancies between results were usually attributed to the purity of the tested compound, the experimental setup, the operator’s experience, or other experimental parameters (<xref rid="B4" ref-type="bibr">Ateba et al., 2018</xref>). Many of related pathologies or conditions such as antimicrobial resistance, cancer, diabetes mellitus, and neurodegenerative diseases are becoming pivotal concerns for public health over the world. However, although AIF might be considered a promising preventive and/or therapeutic agent for such ailments, these investigations are only at the beginning. Using suitable and well-designed standardized models or assays, further and thorough studies related to the above mentioned or other pathologies/conditions are needed to confirm this potential. <italic>In vitro</italic> evaluation is an important primary screen and due to its rapidity common practice in many research laboratories. Nevertheless, many <italic>in vitro</italic> studies are not necessarily optimal due to poor standardization, redundancy, and/or outdated methodology (<xref rid="B124" ref-type="bibr">Tan and Lim, 2015</xref>). Clearly, compounds exhibiting promising activity require further studies to validate or confirm their therapeutic potential (<xref rid="B55" ref-type="bibr">Kenny et al., 2015</xref>). Accordingly, the correlation with <italic>in vivo</italic> data using appropriate models is an indispensable prerequisite.</p><p>The analysis of structure–activity relationships provides information on the preferential conformation to maintain high activities. Studies of AIF until now revealed that the free –OH groups at C-4′ and C-5 are important for the fungicidal activity towards <italic>C. albicans</italic> (<xref rid="B5" ref-type="bibr">Ayine-Tora et al., 2016</xref>). 4′-O-Methylation and the presence of a prenyl group at C-8 enhanced anticancer activities (<xref rid="B75" ref-type="bibr">Liu et al., 2009</xref>; <xref rid="B50" ref-type="bibr">Hu et al., 2017</xref>). Studies with diversified substituents would be ideal for the investigation of SARs. They might allow the identification of important structures with reduced toxicity and increased therapeutic efficacy that can guide the design of novel leads or drug candidates. However, such studies on AIF and its derivatives are scarce until now, and this underlines the necessity of further well-performed investigations.</p><p>Besides the efficacy, extensive safety and pharmacokinetic data are required for potential drug candidates as an important aspect in the drug development process. However, till today, no study dealing with the toxicity or pharmacokinetics of AIF has been reported.</p></sec><sec sec-type="conclusions" id="s5"><title>Conclusion</title><p>This review evidences that AIF is a versatile compound with a wide array of possible health benefits. We summarize the current preclinical evidence of the antiosteoporotic, antioxidant and anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective activities (<xref ref-type="fig" rid="f2"><bold>Figure 2</bold></xref>). However, more persuasive and scientific evidence and detailed mechanistic studies are urgently needed for a therapeutic exploitation of AIF. Moreover, SAR of AIF and its derivatives indicates that 4′-O-methyl-AIF appears to be more promising than AIF, and these indications need to be investigated in-depth.</p><fig id="f2" position="float"><label>Figure 2</label><caption><p>Overview over pharmacological activities of alpinumisoflavone and some of its derivatives.</p></caption><graphic xlink:href="fphar-10-00952-g002"></graphic></fig></sec><sec id="s6"><title>Author Contributions</title><p>SA obtained literatures, wrote the first draft, and edited the manuscript; MM obtained literatures and wrote sections of the manuscript. SD, SZ, and DN gave ideas and critically reviewed the manuscript. LK gave ideas, critically reviewed and edited the manuscript. All authors read and approved the manuscript.</p></sec><sec id="s7"><title>Conflict of Interest Statement</title><p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec></body><back><ref-list><title>References</title><ref id="B1"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akter</surname><given-names>K.</given-names></name><name><surname>Barnes</surname><given-names>E. C.</given-names></name><name><surname>Loa-Kum-Cheung</surname><given-names>W. L.</given-names></name><name><surname>Yin</surname><given-names>P.</given-names></name><name><surname>Kichu</surname><given-names>M.</given-names></name><name><surname>Brophy</surname><given-names>J. J.</given-names></name><etal></etal></person-group> (<year>2016</year>). <article-title>Antimicrobial and antioxidant activity and chemical characterization of <italic>Erythrina stricta</italic> Roxb. (Fabaceae)</article-title>. <source>J. Ethnopharmacol.</source><volume>185</volume>, <fpage>171</fpage>–<lpage>181</lpage>. <pub-id pub-id-type="doi">10.1016/j.jep.2016.03.011</pub-id><pub-id pub-id-type="pmid">26969405</pub-id></mixed-citation></ref><ref id="B2"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Altaf</surname><given-names>M.</given-names></name><name><surname>Miller</surname><given-names>C. H.</given-names></name><name><surname>Bellows</surname><given-names>D. S.</given-names></name><name><surname>O’Toole</surname><given-names>R.</given-names></name></person-group> (<year>2010</year>). <article-title>Evaluation of the <italic>Mycobacterium smegmatis</italic> and BCG models for the discovery of <italic>Mycobacterium tuberculosis</italic> inhibitors</article-title>. <source>Tuberculosis</source><volume>90</volume>, <fpage>333</fpage>–<lpage>337</lpage>. <pub-id pub-id-type="doi">10.1016/j.tube.2010.09.002</pub-id><pub-id pub-id-type="pmid">20933470</pub-id></mixed-citation></ref><ref id="B3"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amen</surname><given-names>Y. M.</given-names></name><name><surname>Marzouk</surname><given-names>A. M.</given-names></name><name><surname>Zaghloul</surname><given-names>M. G.</given-names></name><name><surname>Afifi</surname><given-names>M. S.</given-names></name></person-group> (<year>2013</year>). <article-title>Bioactive compounds from <italic>Tipuana tipu</italic> growing in Egypt</article-title>. <source>J. Am. Sci.</source><volume>9</volume> (<issue>10</issue>), <fpage>334</fpage>–<lpage>339</lpage>.</mixed-citation></ref><ref id="B4"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ateba</surname><given-names>S. B.</given-names></name><name><surname>Mvondo</surname><given-names>M. A.</given-names></name><name><surname>Tchoukouegno Ngueu</surname><given-names>S.</given-names></name><name><surname>Tchoumtchoua</surname><given-names>J.</given-names></name><name><surname>Awounfack</surname><given-names>C.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Natural terpenoids against female breast cancer: a 5-year recent research</article-title>. <source>Curr. Med. Chem.</source><volume>25</volume>, <fpage>3162</fpage>–<lpage>3213</lpage>. <pub-id pub-id-type="doi">10.2174/0929867325666180214110932</pub-id><pub-id pub-id-type="pmid">29446727</pub-id></mixed-citation></ref><ref id="B5"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ayine-Tora</surname><given-names>D. M.</given-names></name><name><surname>Kingsford-Adaboh</surname><given-names>R.</given-names></name><name><surname>Asomaning</surname><given-names>W. A.</given-names></name><name><surname>Harrison</surname><given-names>J. J. E. K.</given-names></name><name><surname>Mills-Robertson</surname><given-names>F. C.</given-names></name><name><surname>Bukari</surname><given-names>Y.</given-names></name><etal></etal></person-group> (<year>2016</year>). <article-title>Coumarin antifungal lead compounds from <italic>Millettia thonningii</italic> and their predicted mechanism of action</article-title>. <source>Molecules</source><volume>21</volume> (<issue>10</issue>), <fpage>1369</fpage>. <pub-id pub-id-type="doi">10.3390/molecules21101369</pub-id></mixed-citation></ref><ref id="B6"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Balouiri</surname><given-names>M.</given-names></name><name><surname>Sadiki</surname><given-names>M.</given-names></name><name><surname>Ibnsouda</surname><given-names>S. K.</given-names></name></person-group> (<year>2016</year>). <article-title>Methods for <italic>in vitro</italic> evaluating antimicrobial activity: a review</article-title>. <source>J. Pharm. Anal.</source><volume>6</volume>, <fpage>71</fpage>–<lpage>79</lpage>. <pub-id pub-id-type="doi">10.1016/j.jpha.2015.11.005</pub-id><pub-id pub-id-type="pmid">29403965</pub-id></mixed-citation></ref><ref id="B7"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ben-David</surname><given-names>U.</given-names></name><name><surname>Ha</surname><given-names>G.</given-names></name><name><surname>Tseng</surname><given-names>Y.-Y.</given-names></name><name><surname>Greenwald</surname><given-names>N. F.</given-names></name><name><surname>Oh</surname><given-names>C.</given-names></name><name><surname>Shih</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Patient-derived xenografts undergo mouse-specific tumor evolution</article-title>. <source>Nature Genetics</source><volume>49</volume>, <fpage>1567</fpage>–<lpage>1578</lpage>. <pub-id pub-id-type="doi">10.1038/ng.3967</pub-id><pub-id pub-id-type="pmid">28991255</pub-id></mixed-citation></ref><ref id="B8"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Benzie</surname><given-names>I. F. F.</given-names></name><name><surname>Strain</surname><given-names>J. J.</given-names></name></person-group> (<year>1999</year>). <article-title>Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration</article-title>. <source>Methods Enzymol.</source><volume>299</volume>, <fpage>15</fpage>–<lpage>27</lpage>. <pub-id pub-id-type="doi">10.1016/S0076-6879(99)99005-5</pub-id><pub-id pub-id-type="pmid">9916193</pub-id></mixed-citation></ref><ref id="B9"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bernini</surname><given-names>R.</given-names></name><name><surname>Crisante</surname><given-names>F.</given-names></name><name><surname>Ginnasi</surname><given-names>M. C.</given-names></name></person-group> (<year>2011</year>). <article-title>A convenient and safe O-methylation of flavonoids with dimethyl carbonate (DMC)</article-title>. <source>Molecules</source><volume>16</volume>, <fpage>1418</fpage>–<lpage>1425</lpage>. <pub-id pub-id-type="doi">10.3390/molecules16021418</pub-id><pub-id pub-id-type="pmid">21307820</pub-id></mixed-citation></ref><ref id="B10"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Boik</surname><given-names>J.</given-names></name></person-group> (<year>2001</year>). <source>Natural compounds in cancer therapy. 1st edition</source>. <publisher-loc>Minnesota</publisher-loc>: <publisher-name>Oregon Medical Press</publisher-name>.</mixed-citation></ref><ref id="B11"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bórquez</surname><given-names>J.</given-names></name><name><surname>Kennelly</surname><given-names>E. J.</given-names></name><name><surname>Simirgiotis</surname><given-names>M. J.</given-names></name></person-group> (<year>2013</year>). <article-title>Activity guided isolation of isoflavones and hyphenated HPLC-PDA-ESI-ToF-MS metabolome profiling of <italic>Azorella madreporica</italic> Clos. from northern Chile</article-title>. <source>Food Res. Int.</source><volume>52</volume>, <fpage>288</fpage>–<lpage>297</lpage>. <pub-id pub-id-type="doi">10.1016/j.foodres.2013.02.055</pub-id></mixed-citation></ref><ref id="B12"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Botta</surname><given-names>B.</given-names></name><name><surname>Menendez</surname><given-names>P.</given-names></name><name><surname>Zappia</surname><given-names>G.</given-names></name><name><surname>de Lima</surname><given-names>R. A.</given-names></name><name><surname>Torge</surname><given-names>R.</given-names></name><name><surname>Monache</surname><given-names>G. D.</given-names></name></person-group> (<year>2009</year>). <article-title>Prenylated isoflavonoids: botanical distribution, structures, biological activities and biotechnological studies. An update (1995–2006)</article-title>. <source>Curr. Med. Chem.</source><volume>16</volume>, <fpage>3414</fpage>–<lpage>3468</lpage>. <pub-id pub-id-type="doi">10.2174/092986709789057662</pub-id><pub-id pub-id-type="pmid">19548871</pub-id></mixed-citation></ref><ref id="B13"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Botta</surname><given-names>B.</given-names></name><name><surname>Vitali</surname><given-names>A.</given-names></name><name><surname>Menendez</surname><given-names>P.</given-names></name><name><surname>Misiti</surname><given-names>D.</given-names></name><name><surname>Monache</surname><given-names>G. D.</given-names></name></person-group> (<year>2005</year>). <article-title>Prenylated flavonoids: pharmacology and biotechnology</article-title>. <source>Curr. Med. Chem.</source><volume>12</volume>, <fpage>713</fpage>–<lpage>739</lpage>. <pub-id pub-id-type="doi">10.2174/0929867053202241</pub-id></mixed-citation></ref><ref id="B14"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaturvedi</surname><given-names>V.</given-names></name><name><surname>Dwivedi</surname><given-names>N.</given-names></name><name><surname>Tripathi</surname><given-names>R. P.</given-names></name><name><surname>Sinha</surname><given-names>S.</given-names></name></person-group> (<year>2007</year>). <article-title>Evaluation of <italic>Mycobacterium smegmatis</italic> as a possible surrogate screen for selecting molecules active against multi-drug resistant <italic>Mycobacterium tuberculosis</italic></article-title>. <source>J. Gen. Appl. Microbiol.</source><volume>53</volume>, <fpage>333</fpage>–<lpage>337</lpage>. <pub-id pub-id-type="doi">10.2323/jgam.53.333</pub-id><pub-id pub-id-type="pmid">18187888</pub-id></mixed-citation></ref><ref id="B15"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaudhury</surname><given-names>A.</given-names></name><name><surname>Duvoor</surname><given-names>C.</given-names></name><name><surname>Reddy Dendi</surname><given-names>V. S.</given-names></name><name><surname>Kraleti</surname><given-names>S.</given-names></name><name><surname>Chada</surname><given-names>A.</given-names></name><name><surname>Ravilla</surname><given-names>R.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management</article-title>. <source>Front. Endocrinol.</source><volume>8</volume>, <fpage>6</fpage>. <pub-id pub-id-type="doi">10.3389/fendo.2017.00006</pub-id></mixed-citation></ref><ref id="B16"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>L. W.</given-names></name><name><surname>Cheng</surname><given-names>M. J.</given-names></name><name><surname>Peng</surname><given-names>C. F.</given-names></name><name><surname>Chen</surname><given-names>I. S.</given-names></name></person-group> (<year>2010</year>). <article-title>Secondary metabolites and antimycobacterial activities from the roots of <italic>Ficus nervosa</italic></article-title>. <source>Chem. Biodivers.</source><volume>7</volume>, <fpage>1814</fpage>–<lpage>1821</lpage>. <pub-id pub-id-type="doi">10.1002/cbdv.200900227</pub-id><pub-id pub-id-type="pmid">20658670</pub-id></mixed-citation></ref><ref id="B17"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>X.</given-names></name><name><surname>Mukwaya</surname><given-names>E.</given-names></name><name><surname>Wong</surname><given-names>M. S.</given-names></name><name><surname>Zhang</surname><given-names>Y.</given-names></name></person-group> (<year>2014</year>). <article-title>A systematic review on biological activities of prenylated flavonoids</article-title>. <source>Pharm. Biol.</source><volume>52</volume>, <fpage>655</fpage>–<lpage>660</lpage>. <pub-id pub-id-type="doi">10.3109/13880209.2013.853809</pub-id><pub-id pub-id-type="pmid">24256182</pub-id></mixed-citation></ref><ref id="B18"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chukwujekwu</surname><given-names>J. C.</given-names></name><name><surname>Van Heerden</surname><given-names>F. R.</given-names></name><name><surname>Van Staden</surname><given-names>J.</given-names></name></person-group> (<year>2011</year>). <article-title>Antibacterial activity of flavonoids from the stem bark of <italic>Erythrina caffra</italic> Thunb</article-title>. <source>Phytother. Res.</source><volume>25</volume>, <fpage>46</fpage>–<lpage>48</lpage>. <pub-id pub-id-type="doi">10.1002/ptr.3159</pub-id><pub-id pub-id-type="pmid">20623615</pub-id></mixed-citation></ref><ref id="B19"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Číž</surname><given-names>M.</given-names></name><name><surname>Čížová</surname><given-names>H.</given-names></name><name><surname>Denev</surname><given-names>P.</given-names></name><name><surname>Kratchanova</surname><given-names>M.</given-names></name><name><surname>Slavov</surname><given-names>A.</given-names></name><name><surname>Lojek</surname><given-names>A.</given-names></name></person-group> (<year>2010</year>). <article-title>Different methods for control and comparison of the antioxidant properties of vegetables</article-title>. <source>Food Control</source><volume>21</volume> (<issue>4</issue>), <fpage>518</fpage>–<lpage>523</lpage>. <pub-id pub-id-type="doi">10.1016/j.foodcont.2009.07.017</pub-id></mixed-citation></ref><ref id="B20"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2004</year>). <source>Method for antifungal disk diffusion susceptibility testing of yeasts, approved guideline. CLSI document M44-A</source>. <publisher-loc>Wayne, Pennsylvania 19087-1898, USA</publisher-loc>: <publisher-name>Clincal and Laboratory Standards Institute</publisher-name>, 940 West Valley Road, Suite 1400.</mixed-citation></ref><ref id="B21"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2010</year>a). <source>Method for antifungal disk diffusion susceptibility testing of non-dermatophyte filamentous fungi, approved guideline, CLSI document M51-A</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road, Suite 2500.</mixed-citation></ref><ref id="B22"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2010</year>b). <source>Methods for antimicrobial dilution and disk susceptibility of infrequently isolated or fastidious bacteria, approved guideline, 2nd. ed., CLSI document M45-A2</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road, Suite 2500.</mixed-citation></ref><ref id="B23"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>1998</year>). <source>Methods for determining bactericidal activity of antimicrobial agents, approved guideline, CLSI document M26-A</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road Suite 2500.</mixed-citation></ref><ref id="B24"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2012</year>b). <source>Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, approved standard, 9th ed., CLSI document M07-A9</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road, Suite <fpage>2500</fpage>.</mixed-citation></ref><ref id="B25"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2012</year>a). <source>Performance standards for antimicrobial disk susceptibility tests, approved standard, 7th ed., CLSI document M02-A11</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road, Suite <fpage>2500</fpage>.</mixed-citation></ref><ref id="B26"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2002</year>). <source>Reference method for broth dilution antifungal susceptibility testing of yeasts, approved standard, 2nd ed., NCCLS document M27-A2</source>. <publisher-loc>Wayne, Pennsylvania 19087-1898, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 940 West Valley Road, Suite 1400.</mixed-citation></ref><ref id="B27"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>CLSI</collab></person-group> (<year>2008</year>). <source>Reference method for broth dilution antifungal susceptibility testing filamentous fungi, approved standard, 2nd ed., CLSI document M38-A2</source>. <publisher-loc>Wayne, Pennsylvania 19087, USA</publisher-loc>: <publisher-name>Clinical and Laboratory Standards Institute</publisher-name>, 950 West Valley Road, Suite 2500.</mixed-citation></ref><ref id="B28"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cong</surname><given-names>W.</given-names></name><name><surname>Zhou</surname><given-names>C.</given-names></name><name><surname>Yin</surname><given-names>J.</given-names></name></person-group> (<year>2017</year>). <article-title>Alpinumisoflavone inhibits osteoclast differentiation and exerts anti-osteoporotic effect in ovariectomized mice</article-title>. <source>Biomed. Pharmacother.</source><volume>93</volume>, <fpage>344</fpage>–<lpage>351</lpage>. <pub-id pub-id-type="doi">10.1016/j.biopha.2017.06.059</pub-id><pub-id pub-id-type="pmid">28651235</pub-id></mixed-citation></ref><ref id="B29"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cos</surname><given-names>P.</given-names></name><name><surname>Vlietinck</surname><given-names>A. J.</given-names></name><name><surname>Berghe</surname><given-names>D. V.</given-names></name><name><surname>Maes</surname><given-names>L.</given-names></name></person-group> (<year>2006</year>). <article-title>Anti-infective potential of natural products: how to develop a stronger <italic>in vitro</italic>‘proof-of-concept’</article-title>. <source>J. Ethnopharmacol.</source><volume>106</volume>, <fpage>290</fpage>–<lpage>302</lpage>. <pub-id pub-id-type="doi">10.1016/j.jep.2006.04.003</pub-id><pub-id pub-id-type="pmid">16698208</pub-id></mixed-citation></ref><ref id="B30"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dai</surname><given-names>J.</given-names></name><name><surname>Shen</surname><given-names>D.</given-names></name><name><surname>Yoshida</surname><given-names>W. Y.</given-names></name><name><surname>Parrish</surname><given-names>S. M.</given-names></name><name><surname>Williams</surname><given-names>P. G.</given-names></name></person-group> (<year>2012</year>). <article-title>Isoflavonoids from <italic>Ficus benjamina</italic> and their inhibitory activity on BACE1</article-title>. <source>Planta Med.</source><volume>78</volume>, <fpage>1357</fpage>–<lpage>1362</lpage>. <pub-id pub-id-type="doi">10.1055/s-0032-1315001</pub-id><pub-id pub-id-type="pmid">22763739</pub-id></mixed-citation></ref><ref id="B31"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Dandekar</surname><given-names>A.</given-names></name><name><surname>Mendez</surname><given-names>R.</given-names></name><name><surname>Zhang</surname><given-names>K.</given-names></name></person-group>, (<year>2015</year>). “<article-title>Cross talk between ER Stress, oxidative stress, and inflammation in health and disease</article-title>,” in <source>Stress responses. Methods in molecular biology</source>, vol. <volume>1292</volume> Ed. <person-group person-group-type="author"><name><surname>Oslowski</surname><given-names>C.</given-names></name></person-group> (<publisher-loc>New York, NY</publisher-loc>: <publisher-name>Humana Press</publisher-name>). <pub-id pub-id-type="doi">10.1007/978-1-4939-2522-3_15</pub-id></mixed-citation></ref><ref id="B32"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dendup</surname><given-names>T.</given-names></name><name><surname>Prachyawarakorn</surname><given-names>V.</given-names></name><name><surname>Pansanit</surname><given-names>A.</given-names></name><name><surname>Mahidol</surname><given-names>C.</given-names></name><name><surname>Ruchirawat</surname><given-names>S.</given-names></name><name><surname>Kittakoop</surname><given-names>P.</given-names></name></person-group> (<year>2014</year>). <article-title>α-Glucosidase inhibitory activities of isoflavanones, isoflavones, and pterocarpans from <italic>Mucuna pruriens</italic></article-title>. <source>Planta Med.</source><volume>80</volume>, <fpage>604</fpage>–<lpage>608</lpage>. <pub-id pub-id-type="doi">10.1055/s-0034-1368427</pub-id><pub-id pub-id-type="pmid">24782227</pub-id></mixed-citation></ref><ref id="B33"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Djiogue</surname><given-names>S.</given-names></name><name><surname>Halabalaki</surname><given-names>M.</given-names></name><name><surname>Alexi</surname><given-names>X.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Fomum</surname><given-names>Z. T.</given-names></name><name><surname>Alexis</surname><given-names>M. N.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Isoflavonoids from <italic>Erythrina poeppigiana</italic>: evaluation of their binding affinity for the estrogen receptor</article-title>. <source>J. Nat. Prod.</source><volume>72</volume>, <fpage>1603</fpage>–<lpage>1607</lpage>. <pub-id pub-id-type="doi">10.1021/np900271m</pub-id><pub-id pub-id-type="pmid">19705860</pub-id></mixed-citation></ref><ref id="B34"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Djiogue</surname><given-names>S.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Halabalaki</surname><given-names>M.</given-names></name><name><surname>Kretzschmar</surname><given-names>G.</given-names></name><name><surname>Beyer</surname><given-names>A.</given-names></name><name><surname>Mbanya</surname><given-names>J. C.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Estrogenic properties of naturally occurring prenylated isoflavones in U2OS humanosteosarcoma cells: structure–activity relationships</article-title>. <source>J. Steroid. Biochem. Mol. Biol.</source><volume>120</volume>, <fpage>184</fpage>–<lpage>191</lpage>. <pub-id pub-id-type="doi">10.1016/j.jsbmb.2010.04.014</pub-id><pub-id pub-id-type="pmid">20420908</pub-id></mixed-citation></ref><ref id="B35"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Egermann</surname><given-names>M.</given-names></name><name><surname>Goldhahn</surname><given-names>J.</given-names></name><name><surname>Schneider</surname><given-names>E.</given-names></name></person-group> (<year>2005</year>). <article-title>Animal models for fracture treatment in osteoporosis</article-title>. <source>Osteoporos. Int.</source><volume>16</volume>, <fpage>S129</fpage>–<lpage>S138</lpage>. <pub-id pub-id-type="doi">10.1007/s00198-005-1859-7</pub-id><pub-id pub-id-type="pmid">15750681</pub-id></mixed-citation></ref><ref id="B36"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Edziri</surname><given-names>H.</given-names></name><name><surname>Mastouri</surname><given-names>M.</given-names></name><name><surname>Mahjoub</surname><given-names>M. A.</given-names></name><name><surname>Mighri</surname><given-names>Z.</given-names></name><name><surname>Mahjoub</surname><given-names>A.</given-names></name><name><surname>Verschaeve</surname><given-names>L.</given-names></name></person-group> (<year>2012</year>). <article-title>Antibacterial, antifungal and cytotoxic activities of two flavonoids from <italic>Retama raetam</italic> flowers</article-title>. <source>Molecules</source><volume>17</volume>, <fpage>7284</fpage>–<lpage>7293</lpage>. <pub-id pub-id-type="doi">10.3390/molecules17067284</pub-id><pub-id pub-id-type="pmid">22695233</pub-id></mixed-citation></ref><ref id="B37"><mixed-citation publication-type="journal"><person-group person-group-type="author"><collab>EUCAST Definitive Document</collab></person-group>, <year>2000</year><article-title>Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents</article-title>. <source>Clin. Microbiol. Infec.</source><volume>6</volume> (<issue>9</issue>), <fpage>503</fpage>–<lpage>508</lpage>. <pub-id pub-id-type="doi">10.1046/j.1469-0691.2000.00149.x</pub-id><pub-id pub-id-type="pmid">11168186</pub-id></mixed-citation></ref><ref id="B38"><mixed-citation publication-type="journal"><person-group person-group-type="author"><collab>EUCAST Discussion Document</collab></person-group>, <year>2003</year><article-title>Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution</article-title>. <source>Clin. Microbiol. Infec.</source><volume>9</volume> (<issue>8</issue>), <fpage>1</fpage>–<lpage>7</lpage>. <pub-id pub-id-type="doi">10.1046/j.1469-0691.2003.00790.x</pub-id><pub-id pub-id-type="pmid">12691538</pub-id></mixed-citation></ref><ref id="B39"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Floegel</surname><given-names>A.</given-names></name><name><surname>Kim</surname><given-names>D. O.</given-names></name><name><surname>Chung</surname><given-names>S. J.</given-names></name><name><surname>Koo</surname><given-names>S. I.</given-names></name><name><surname>Chun</surname><given-names>O. K.</given-names></name></person-group> (<year>2011</year>). <article-title>Comparison of ABTS/DPPH assays to measure antioxidant capacity in popular antioxidant-rich US foods</article-title>. <source>J. Food Compos. Anal.</source><volume>24</volume>, <fpage>1043</fpage>–<lpage>1048</lpage>. <pub-id pub-id-type="doi">10.1016/j.jfca.2011.01.008</pub-id></mixed-citation></ref><ref id="B40"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fu</surname><given-names>G.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name><name><surname>Huang</surname><given-names>X.</given-names></name><name><surname>Zhang</surname><given-names>R.</given-names></name><name><surname>Tian</surname><given-names>K.</given-names></name><name><surname>Hou</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Antioxidant and alpha-glucosidase inhibitory activities of isoflavonoids from the rhizomes of <italic>Ficus tikoua</italic></article-title>. <source>Bur. Nat. Prod. Res.</source><volume>32</volume>, <fpage>399</fpage>–<lpage>405</lpage>. <pub-id pub-id-type="doi">10.1080/14786419.2017.1312391</pub-id><pub-id pub-id-type="pmid">28423925</pub-id></mixed-citation></ref><ref id="B41"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gao</surname><given-names>M.</given-names></name><name><surname>Chang</surname><given-names>Y.</given-names></name><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Ban</surname><given-names>C.</given-names></name><name><surname>Zhang</surname><given-names>F.</given-names></name></person-group> (<year>2017</year>). <article-title>Reduction of COX-2 through modulating miR-124/SPHK1 axis contributes to the antimetastatic effect of alpinumisoflavone in melanoma</article-title>. <source>Am. J. Transl. Res.</source><volume>9</volume>, <fpage>986</fpage>–<lpage>998</lpage>.<pub-id pub-id-type="pmid">28386327</pub-id></mixed-citation></ref><ref id="B42"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>Guangxi Institute of Chinese Medicine, Pharmaceutical Science</collab></person-group> (<year>1986</year>). <source>Medicinal plants directory of Guangxi</source>. <publisher-loc>Guangxi</publisher-loc>: <publisher-name>Guangxi People’s Publishing House</publisher-name>, <fpage>232</fpage>.</mixed-citation></ref><ref id="B43"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Han</surname><given-names>X. H.</given-names></name><name><surname>Hong</surname><given-names>S. S.</given-names></name><name><surname>Hwang</surname><given-names>J. S.</given-names></name><name><surname>Jeong</surname><given-names>S. H.</given-names></name><name><surname>Hwang</surname><given-names>J. H.</given-names></name><name><surname>Lee</surname><given-names>M. H.</given-names></name><etal></etal></person-group> (<year>2005</year>). <article-title>Monoamine oxidase inhibitory constituents from the fruits of <italic>Cudrania tricuspidata</italic></article-title>. <source>Arch. Pharm. Res.</source><volume>28</volume>, <fpage>1324</fpage>–<lpage>1327</lpage>. <pub-id pub-id-type="doi">10.1007/BF02977895</pub-id><pub-id pub-id-type="pmid">16392662</pub-id></mixed-citation></ref><ref id="B44"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Han</surname><given-names>Y.</given-names></name><name><surname>Yang</surname><given-names>X.</given-names></name><name><surname>Zhao</surname><given-names>N.</given-names></name><name><surname>Peng</surname><given-names>J.</given-names></name><name><surname>Gao</surname><given-names>H.</given-names></name><name><surname>Qiu</surname><given-names>X.</given-names></name></person-group> (<year>2016</year>). <article-title>Alpinumisoflavone induces apoptosis in esophageal squamous cell carcinoma by modulating miR-370/PIM1 signaling</article-title>. <source>Am. J. Cancer Res.</source><volume>6</volume>, <fpage>2755</fpage>–<lpage>2771</lpage>.<pub-id pub-id-type="pmid">28042498</pub-id></mixed-citation></ref><ref id="B45"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Heikkila</surname><given-names>R. E.</given-names></name><name><surname>Sonsalla</surname><given-names>P. K.</given-names></name><name><surname>Duvoisin</surname><given-names>R. C.</given-names></name></person-group> (<year>1989</year>). “<article-title>Biochemical models of Parkinson</article-title>’s disease,” in <source>Drugs as tools in neurotransmitter research. Neuromethods</source>, vol. <volume>12</volume> Eds. <person-group person-group-type="editor"><name><surname>Boulton</surname><given-names>A. A.</given-names></name><name><surname>Baker</surname><given-names>G. B.</given-names></name><name><surname>Juorio</surname><given-names>A. V.</given-names></name></person-group> (<publisher-loc>Totowa, New Jersey</publisher-loc>: <publisher-name>Humana Press</publisher-name>).</mixed-citation></ref><ref id="B46"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hendrickx</surname><given-names>G.</given-names></name><name><surname>Boudin</surname><given-names>E.</given-names></name><name><surname>Van Hul</surname><given-names>W.</given-names></name></person-group> (<year>2015</year>). <article-title>A look behind the scenes: the risk and pathogenesis of primary osteoporosis</article-title>. <source>Nat. Rev. Rheumatol.</source><volume>11</volume>:<fpage>462</fpage>–<lpage>474</lpage>. <pub-id pub-id-type="doi">10.1038/nrrheum.2015.48</pub-id><pub-id pub-id-type="pmid">25900210</pub-id></mixed-citation></ref><ref id="B47"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hiep</surname><given-names>N. T.</given-names></name><name><surname>Kwon</surname><given-names>J.</given-names></name><name><surname>Kim</surname><given-names>D.-W.</given-names></name><name><surname>Hwang</surname><given-names>B. Y.</given-names></name><name><surname>Lee</surname><given-names>H.-J.</given-names></name><name><surname>Mar</surname><given-names>W.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Isoflavones with neuroprotective activities from fruits of <italic>Cudrania tricuspidata</italic></article-title>. <source>Phytochemistry</source><volume>111</volume>, <fpage>141</fpage>–<lpage>148</lpage>. <pub-id pub-id-type="doi">10.1016/j.phytochem.2014.10.021</pub-id><pub-id pub-id-type="pmid">25487308</pub-id></mixed-citation></ref><ref id="B48"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hiep</surname><given-names>N. T.</given-names></name><name><surname>Kwon</surname><given-names>J.</given-names></name><name><surname>Kim</surname><given-names>D.-W.</given-names></name><name><surname>Hong</surname><given-names>S.</given-names></name><name><surname>Guo</surname><given-names>Y.</given-names></name><name><surname>Hwang</surname><given-names>B. Y.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Neuroprotective constituents from the fruits of <italic>Maclura tricuspidata</italic></article-title>. <source>Tetrahedron</source><volume>73</volume>, <fpage>2747</fpage>–<lpage>2759</lpage>. <pub-id pub-id-type="doi">10.1016/j.tet.2017.03.064</pub-id></mixed-citation></ref><ref id="B49"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>S.</given-names></name><name><surname>Kwon</surname><given-names>J.</given-names></name><name><surname>Hiep</surname><given-names>N. T.</given-names></name><name><surname>Sim</surname><given-names>S. J.</given-names></name><name><surname>Kim</surname><given-names>N.</given-names></name><name><surname>Kim</surname><given-names>K. H.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>The isoflavones and extracts from <italic>Maclura tricuspidata</italic> fruit protect against neuronal cell death in ischemic injury <italic>via</italic> induction of Nox4-targeting miRNA-25, miRNA-92a, and miRNA-146a</article-title>. <source>J. Funct. Foods</source><volume>40</volume>, <fpage>785</fpage>–<lpage>797</lpage>. <pub-id pub-id-type="doi">10.1016/j.jff.2017.12.011</pub-id></mixed-citation></ref><ref id="B50"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>Z.</given-names></name><name><surname>Wang</surname><given-names>L.</given-names></name><name><surname>Deng</surname><given-names>L.</given-names></name><name><surname>Sun</surname><given-names>J.</given-names></name><name><surname>Jiang</surname><given-names>X.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Scandenolone, a natural isoflavone derivative from <italic>Cudrania tricuspidata</italic> fruit, targets EGFR to induce apoptosis and block autophagy flux in human melanoma cells</article-title>. <source>J. Funct. Foods</source><volume>37</volume>, <fpage>229</fpage>–<lpage>240</lpage>. <pub-id pub-id-type="doi">10.1016/j.jff.2017.07.055</pub-id></mixed-citation></ref><ref id="B51"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>D.</given-names></name><name><surname>Ou</surname><given-names>B.</given-names></name><name><surname>Prior</surname><given-names>R. L.</given-names></name></person-group> (<year>2005</year>). <article-title>The chemistry behind antioxidant capacity assays</article-title>. <source>J. Agric. Food Chem.</source><volume>53</volume>, <fpage>1841</fpage>–<lpage>1856</lpage>. <pub-id pub-id-type="doi">10.1021/jf030723c</pub-id><pub-id pub-id-type="pmid">15769103</pub-id></mixed-citation></ref><ref id="B52"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ito</surname><given-names>C.</given-names></name><name><surname>Itoigawa</surname><given-names>M.</given-names></name><name><surname>Tan</surname><given-names>H. T. W.</given-names></name><name><surname>Tokuda</surname><given-names>H.</given-names></name><name><surname>Mou</surname><given-names>X. Y.</given-names></name><name><surname>Mukainaka</surname><given-names>T.</given-names></name><etal></etal></person-group> (<year>2000</year>). <article-title>Anti-tumor-promoting effects of isoflavonoids on Epstein–Barr virus activation and two-stage mouse skin carcinogenesis</article-title>. <source>Cancer Lett.</source><volume>152</volume>, <fpage>187</fpage>–<lpage>192</lpage>. <pub-id pub-id-type="doi">10.1016/S0304-3835(00)00331-1</pub-id><pub-id pub-id-type="pmid">10773411</pub-id></mixed-citation></ref><ref id="B53"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jackson</surname><given-names>B.</given-names></name><name><surname>Owen</surname><given-names>P. J.</given-names></name><name><surname>Scheinmann</surname><given-names>F.</given-names></name></person-group> (<year>1971</year>). <article-title>Extractives from poisonous British plants. Part I. The structure of alpinumisoflavone, a new pyranoisoflavone from <italic>Laburnum alpinum</italic></article-title>. <source>J. Presl. J. Chem. Soc. C</source><volume>0</volume>, <fpage>3389</fpage>–<lpage>3392</lpage>. <pub-id pub-id-type="doi">10.1039/j39710003389</pub-id></mixed-citation></ref><ref id="B54"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jorgensen</surname><given-names>J. H.</given-names></name><name><surname>Ferraro</surname><given-names>M. J.</given-names></name></person-group> (<year>2009</year>). <article-title>Antimicrobial susceptibility testing: a review of general principles and contemporary practices</article-title>. <source>Clin. Infect. Dis.</source><volume>49</volume>, <fpage>1749</fpage>–<lpage>1755</lpage>. <pub-id pub-id-type="doi">10.1086/647952</pub-id><pub-id pub-id-type="pmid">19857164</pub-id></mixed-citation></ref><ref id="B55"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kenny</surname><given-names>C. R.</given-names></name><name><surname>Furey</surname><given-names>A.</given-names></name><name><surname>Lucey</surname><given-names>B.</given-names></name></person-group> (<year>2015</year>). <article-title>A post-antibiotic era looms: can plant natural product research fill the void</article-title>? <source>Br. J. Biomed. Sci.</source><volume>72</volume>, <fpage>191</fpage>–<lpage>200</lpage>. <pub-id pub-id-type="doi">10.1080/09674845.2015.11665752</pub-id><pub-id pub-id-type="pmid">26738402</pub-id></mixed-citation></ref><ref id="B56"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Khalid</surname><given-names>S. A.</given-names></name><name><surname>Farouk</surname><given-names>A.</given-names></name><name><surname>Geary</surname><given-names>T. G.</given-names></name><name><surname>Jensen</surname><given-names>J. B.</given-names></name></person-group> (<year>1986</year>). <article-title>Potential antimalarial candidates from African plants: an <italic>in vitro</italic> approach using <italic>Plasmodium falciparum</italic></article-title>. <source>J. Ethnopharmacol.</source><volume>15</volume>, <fpage>201</fpage>–<lpage>209</lpage>. <pub-id pub-id-type="doi">10.1016/0378-8741(86)90156-X</pub-id><pub-id pub-id-type="pmid">3520157</pub-id></mixed-citation></ref><ref id="B57"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>D. W.</given-names></name><name><surname>Kwon</surname><given-names>J.</given-names></name><name><surname>Sim</surname><given-names>S. J.</given-names></name><name><surname>Lee</surname><given-names>D.</given-names></name><name><surname>Mar</surname><given-names>W.</given-names></name></person-group> (<year>2017</year>). <article-title>Orobol derivatives and extracts from <italic>Cudrania tricuspidata</italic> fruits protect against 6-hydroxydopamine-induced neuronal cell death by enhancing proteasome activity and the ubiquitin/proteasome-dependent degradation of α-synuclein and synphilin-1</article-title>. <source>J. Funct. Foods</source><volume>29</volume>, <fpage>104</fpage>–<lpage>114</lpage>. <pub-id pub-id-type="doi">10.1016/j.jff.2016.12.017</pub-id></mixed-citation></ref><ref id="B58"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuete</surname><given-names>V.</given-names></name><name><surname>Mbaveng</surname><given-names>A. T.</given-names></name><name><surname>Nono</surname><given-names>E. C. N.</given-names></name><name><surname>Simo</surname><given-names>C. C.</given-names></name><name><surname>Zeino</surname><given-names>M.</given-names></name><name><surname>Nkengfack</surname><given-names>A. E.</given-names></name><etal></etal></person-group> (<year>2016</year>). <article-title>Cytotoxicity of seven naturally occurring phenolic compounds towards multi-factorial drug-resistant cancer cells</article-title>. <source>Phytomedicine</source><volume>23</volume>, <fpage>856</fpage>–<lpage>863</lpage>. <pub-id pub-id-type="doi">10.1016/j.phymed.2016.04.007</pub-id><pub-id pub-id-type="pmid">27288921</pub-id></mixed-citation></ref><ref id="B59"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuete</surname><given-names>V.</given-names></name><name><surname>Ngameni</surname><given-names>B.</given-names></name><name><surname>Fotso Simo</surname><given-names>C. C.</given-names></name><name><surname>Kengap Tankeu</surname><given-names>R.</given-names></name><name><surname>Tchaleu Ngadjui</surname><given-names>B.</given-names></name><name><surname>Meyer</surname><given-names>J. J. M.</given-names></name><etal></etal></person-group> (<year>2008</year>). <article-title>Antimicrobial activity of the crude extracts and compounds from <italic>Ficus chlamydocarpa</italic> and <italic>Ficus cordata</italic> (Moraceae)</article-title>. <source>J. Ethnopharmacol.</source><volume>120</volume>, <fpage>17</fpage>–<lpage>24</lpage>. <pub-id pub-id-type="doi">10.1016/j.jep.2008.07.026</pub-id><pub-id pub-id-type="pmid">18718518</pub-id></mixed-citation></ref><ref id="B60"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>S.</given-names></name><name><surname>Pandey</surname><given-names>A. K.</given-names></name></person-group> (<year>2013</year>). <article-title>Chemistry and biological activities of flavonoids: an overview</article-title>. <source>Sci. World J.</source><volume>2013</volume>, <fpage>162750</fpage>. <pub-id pub-id-type="doi">10.1155/2013/162750</pub-id></mixed-citation></ref><ref id="B61"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kumar</surname><given-names>S.</given-names></name><name><surname>Pathania</surname><given-names>A. S.</given-names></name><name><surname>Saxena</surname><given-names>A. K.</given-names></name><name><surname>Vishwakarma</surname><given-names>R. A.</given-names></name><name><surname>Ali</surname><given-names>A.</given-names></name><name><surname>Bhushan</surname><given-names>S.</given-names></name></person-group> (<year>2013</year>). <article-title>The anticancer potential of flavonoids isolated from the stem bark of <italic>Erythrina suberosa</italic> through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells</article-title>. <source>Chem-Biol. Interact.</source><volume>205</volume>, <fpage>128</fpage>–<lpage>137</lpage>. <pub-id pub-id-type="doi">10.1016/j.cbi.2013.06.020</pub-id><pub-id pub-id-type="pmid">23850732</pub-id></mixed-citation></ref><ref id="B62"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lambert</surname><given-names>M. N. T.</given-names></name><name><surname>Jeppesen</surname><given-names>P. B.</given-names></name></person-group> (<year>2018</year>). <article-title>Isoflavones and bone health in perimenopausal and postmenopausal women</article-title>. <source>Curr. Opin. Clin. Nutr.</source><volume>21</volume>, <fpage>475</fpage>–<lpage>480</lpage>. <pub-id pub-id-type="doi">10.1097/MCO.0000000000000513</pub-id></mixed-citation></ref><ref id="B63"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Landgraf</surname><given-names>M.</given-names></name><name><surname>McGovern</surname><given-names>J. A.</given-names></name><name><surname>Fried</surname><given-names>P.</given-names></name><name><surname>Hutmacher</surname><given-names>D. W.</given-names></name></person-group> (<year>2018</year>). <article-title>Rational design of mouse models for cancer research</article-title>. <source>Trends Biotechnol.</source><volume>36</volume>, <fpage>242</fpage>–<lpage>251</lpage>. <pub-id pub-id-type="doi">10.1016/j.tibtech.2017.12.001</pub-id><pub-id pub-id-type="pmid">29310843</pub-id></mixed-citation></ref><ref id="B64"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lapčík</surname><given-names>O.</given-names></name></person-group> (<year>2007</year>). <article-title>Isoflavonoids in non-leguminous taxa: a rarity or a rule</article-title>? <source>Phytochemistry</source><volume>68</volume>, <fpage>2909</fpage>–<lpage>2916</lpage>. <pub-id pub-id-type="doi">10.1016/j.phytochem.2007.08.006</pub-id><pub-id pub-id-type="pmid">17904596</pub-id></mixed-citation></ref><ref id="B65"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>J. S.</given-names></name><name><surname>Oh</surname><given-names>W. K.</given-names></name><name><surname>Ahn</surname><given-names>J. S.</given-names></name><name><surname>Kim</surname><given-names>Y. H.</given-names></name><name><surname>Mbafor</surname><given-names>J. T.</given-names></name><name><surname>Wandji</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2009</year>a). <article-title>Prenylisoflavonoids from <italic>Erythrina senegalensis</italic> as novel HIV-1 protease inhibitors</article-title>. <source>Planta Med.</source><volume>75</volume>, <fpage>268</fpage>–<lpage>270</lpage>. <pub-id pub-id-type="doi">10.1055/s-0028-1088395</pub-id><pub-id pub-id-type="pmid">19097000</pub-id></mixed-citation></ref><ref id="B66"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>M. S.</given-names></name><name><surname>Kim</surname><given-names>C. H.</given-names></name><name><surname>Hoang</surname><given-names>D. M.</given-names></name><name><surname>Kim</surname><given-names>B. Y.</given-names></name><name><surname>Sohn</surname><given-names>C. B.</given-names></name><name><surname>Kim</surname><given-names>M. R.</given-names></name><etal></etal></person-group> (<year>2009</year>b). <article-title>Genistein derivatives from <italic>Tetracera scandens</italic> stimulate glucose-uptake in L6 myotubes</article-title>. <source>Biol. Pharm. Bull.</source><volume>32</volume>, <fpage>504</fpage>–<lpage>508</lpage>. <pub-id pub-id-type="doi">10.1248/bpb.32.504</pub-id><pub-id pub-id-type="pmid">19252305</pub-id></mixed-citation></ref><ref id="B67"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Legler</surname><given-names>J.</given-names></name><name><surname>van den Brink</surname><given-names>C. E.</given-names></name><name><surname>Brouwer</surname><given-names>A.</given-names></name><name><surname>Murk</surname><given-names>A. J.</given-names></name><name><surname>van der Saag</surname><given-names>P. T.</given-names></name><name><surname>Vethaak</surname><given-names>A. D.</given-names></name><etal></etal></person-group> (<year>1999</year>). <article-title>Development of a stably transfected estrogen receptor-mediated luciferase reporter gene assay in the human T47D breast cancer cell line</article-title>. <source>Toxicol. Sci.</source><volume>48</volume>, <fpage>55</fpage>–<lpage>66</lpage>. <pub-id pub-id-type="doi">10.1093/toxsci/48.1.55</pub-id><pub-id pub-id-type="pmid">10330684</pub-id></mixed-citation></ref><ref id="B68"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lelovas</surname><given-names>P. P.</given-names></name><name><surname>Xanthos</surname><given-names>T. T.</given-names></name><name><surname>Thoma</surname><given-names>S. E.</given-names></name><name><surname>Lyritis</surname><given-names>G. P.</given-names></name><name><surname>Dontas</surname><given-names>I. A.</given-names></name></person-group> (<year>2008</year>). <article-title>The laboratory rat as an animal model for osteoporosis research</article-title>. <source>Comparative Med.</source><volume>58</volume>, <fpage>424</fpage>–<lpage>430</lpage>.</mixed-citation></ref><ref id="B69"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Leusch</surname><given-names>F. L.</given-names></name><name><surname>De Jager</surname><given-names>C.</given-names></name><name><surname>Levi</surname><given-names>Y.</given-names></name><name><surname>Lim</surname><given-names>R.</given-names></name><name><surname>Puijker</surname><given-names>L.</given-names></name><name><surname>Sacher</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2010</year>). <article-title>Comparison of five <italic>in vitro</italic> bioassays to measure estrogenic activity in environmental waters</article-title>. <source>Environ. Sci. Technol.</source><volume>44</volume>, <fpage>3853</fpage>–<lpage>3860</lpage>. <pub-id pub-id-type="doi">10.1021/es903899d</pub-id><pub-id pub-id-type="pmid">20423077</pub-id></mixed-citation></ref><ref id="B70"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>D.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Li</surname><given-names>G.</given-names></name><name><surname>Meng</surname><given-names>Y.</given-names></name><name><surname>Jin</surname><given-names>Y.</given-names></name><name><surname>Shang</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2019</year>). <article-title>Alpinumisoflavone causes DNA damage in colorectal cancer cells <italic>via</italic> blocking dna repair mediated by RAD51</article-title>. <source>Life Sci.</source><volume>216</volume>, <fpage>259</fpage>–<lpage>270</lpage>. <pub-id pub-id-type="doi">10.1016/j.lfs.2018.11.032</pub-id><pub-id pub-id-type="pmid">30448264</pub-id></mixed-citation></ref><ref id="B71"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>P. Y.</given-names></name><name><surname>Liang</surname><given-names>Y. C.</given-names></name><name><surname>Sheu</surname><given-names>M. J.</given-names></name><name><surname>Huang</surname><given-names>S. S.</given-names></name><name><surname>Chao</surname><given-names>C. Y.</given-names></name><name><surname>Kuo</surname><given-names>Y. H.</given-names></name><etal></etal></person-group> (<year>2018</year>). <article-title>Alpinumisoflavone attenuates lipopolysaccharide-induced acute lung injury by regulating the effects of anti-oxidation and anti-inflammation both <italic>in vitro</italic> and <italic>in vivo</italic></article-title>. <source>RSC Adv.</source><volume>8</volume>, <fpage>31515</fpage>–<lpage>31528</lpage>. <pub-id pub-id-type="doi">10.1039/C8RA04098B</pub-id></mixed-citation></ref><ref id="B72"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>K.</given-names></name><name><surname>Ji</surname><given-names>S.</given-names></name><name><surname>Song</surname><given-names>W.</given-names></name><name><surname>Kuang</surname><given-names>Y.</given-names></name><name><surname>Lin</surname><given-names>Y.</given-names></name><name><surname>Tang</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Glycybridins A–K, bioactive phenolic compounds from <italic>Glycyrrhiza glabra</italic></article-title>. <source>J. Nat. Prod.</source><volume>80</volume>, <fpage>334</fpage>–<lpage>346</lpage>. <pub-id pub-id-type="doi">10.1021/acs.jnatprod.6b00783</pub-id><pub-id pub-id-type="pmid">28140583</pub-id></mixed-citation></ref><ref id="B73"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>X. C.</given-names></name><name><surname>Joshi</surname><given-names>A. S.</given-names></name><name><surname>ElSohly</surname><given-names>H. N.</given-names></name><name><surname>Khan</surname><given-names>S. I.</given-names></name><name><surname>Jacob</surname><given-names>M. R.</given-names></name><name><surname>Zhang</surname><given-names>Z.</given-names></name><etal></etal></person-group> (<year>2002</year>). <article-title>Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies</article-title>. <source>J. Nat. Prod.</source><volume>65</volume>, <fpage>1909</fpage>–<lpage>1914</lpage>. <pub-id pub-id-type="doi">10.1021/np020289t</pub-id><pub-id pub-id-type="pmid">12502337</pub-id></mixed-citation></ref><ref id="B74"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lim</surname><given-names>J. Y.</given-names></name><name><surname>Hwang</surname><given-names>B. Y.</given-names></name><name><surname>Hwang</surname><given-names>K. W.</given-names></name><name><surname>Park</surname><given-names>S. Y.</given-names></name></person-group> (<year>2012</year>). <article-title>Methylalpinumisoflavone inhibits lipopolysaccharide-induced inflammation in microglial cells by the NF-kappaB and MAPK signaling pathway</article-title>. <source>Phytother. Res.</source><volume>26</volume>, <fpage>1948</fpage>–<lpage>1956</lpage>. <pub-id pub-id-type="doi">10.1002/ptr.4810</pub-id><pub-id pub-id-type="pmid">22899404</pub-id></mixed-citation></ref><ref id="B75"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Veena</surname><given-names>C. K.</given-names></name><name><surname>Brian Morgan</surname><given-names>J.</given-names></name><name><surname>Mohammed</surname><given-names>K. A.</given-names></name><name><surname>Jekabsons</surname><given-names>M. B.</given-names></name><name><surname>Nagle</surname><given-names>D. G.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Methylalpinumisoflavone inhibits hypoxia-inducible factor-1 (HIF-1) activation by simultaneously targeting multiple pathways</article-title>. <source>J. Biol. Chem.</source><volume>284</volume>, <fpage>5859</fpage>–<lpage>5868</lpage>. <pub-id pub-id-type="doi">10.1074/jbc.M806744200</pub-id><pub-id pub-id-type="pmid">19091749</pub-id></mixed-citation></ref><ref id="B76"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lyddiard</surname><given-names>J. R. A.</given-names></name><name><surname>Whitfield</surname><given-names>P. J.</given-names></name><name><surname>Bartl</surname><given-names>A.</given-names></name></person-group> (<year>2002</year>). <article-title>Antischistosomal bioactivity of isoflavonoids from <italic>Millettia thonningii</italic> (Leguminosae)</article-title>. <source>J. Parasitol.</source><volume>88</volume>, <fpage>163</fpage>–<lpage>170</lpage>. <pub-id pub-id-type="doi">10.1645/0022-3395(2002)088[0163:ABOIFM]2.0.CO;2</pub-id><pub-id pub-id-type="pmid">12053958</pub-id></mixed-citation></ref><ref id="B77"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ma</surname><given-names>D. F.</given-names></name><name><surname>Qin</surname><given-names>L. Q.</given-names></name><name><surname>Wang</surname><given-names>P. Y.</given-names></name><name><surname>Katoh</surname><given-names>R.</given-names></name></person-group> (<year>2008</year>). <article-title>Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials</article-title>. <source>Eur. J. Clin. Nutr.</source><volume>62</volume>, <fpage>155</fpage>–<lpage>161</lpage>. <pub-id pub-id-type="doi">10.1038/sj.ejcn.1602748</pub-id><pub-id pub-id-type="pmid">17392695</pub-id></mixed-citation></ref><ref id="B78"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magne Nde</surname><given-names>C. B.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Fomum</surname><given-names>S. T.</given-names></name><name><surname>Wandji</surname><given-names>J.</given-names></name><name><surname>Simpson</surname><given-names>E.</given-names></name><name><surname>Clyne</surname><given-names>C.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title><italic>In vitro</italic> estrogenic activity of two major compounds from the stem bark of <italic>Erythrina lysistemon</italic> (Fabaceae)</article-title>. <source>Eur. J. Pharmacol.</source><volume>674</volume>, <fpage>87</fpage>–<lpage>94</lpage>. <pub-id pub-id-type="doi">10.1016/j.ejphar.2011.10.031</pub-id><pub-id pub-id-type="pmid">22079771</pub-id></mixed-citation></ref><ref id="B79"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magne Nde</surname><given-names>C. B.</given-names></name><name><surname>Zingue</surname><given-names>S.</given-names></name><name><surname>Winter</surname><given-names>E.</given-names></name><name><surname>Creczynski-Pasa</surname><given-names>T. B.</given-names></name><name><surname>Michel</surname><given-names>T.</given-names></name><name><surname>Fernandez</surname><given-names>X.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Flavonoids, breast cancer chemopreventive and/or chemotherapeutic agents</article-title>. <source>Curr. Med. Chem.</source><volume>22</volume>, <fpage>3434</fpage>–<lpage>3446</lpage>. <pub-id pub-id-type="doi">10.2174/0929867322666150729115321</pub-id></mixed-citation></ref><ref id="B80"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Markovski</surname><given-names>A.</given-names></name></person-group> (<year>2016</year>). <article-title>Dynamics of rooting of storehousebush (<italic>Cudrania tricuspidata</italic> (Carrière.) Bur. Ex Lav.). Bur. ex Lav.) cuttings</article-title>. <source>J. Mountain Agri. Balkans</source><volume>19</volume>, <fpage>134</fpage>–<lpage>147</lpage>.</mixed-citation></ref><ref id="B81"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Massoud</surname><given-names>G. N.</given-names></name><name><surname>Li</surname><given-names>W.</given-names></name></person-group> (<year>2015</year>). <article-title>HIF-1α pathway: role, regulation and intervention for cancer therapy</article-title>. <source>Acta Pharm. Sin. B</source><volume>5</volume>, <fpage>378</fpage>–<lpage>389</lpage>. <pub-id pub-id-type="doi">10.1016/j.apsb.2015.05.007</pub-id><pub-id pub-id-type="pmid">26579469</pub-id></mixed-citation></ref><ref id="B82"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Matsuda</surname><given-names>H.</given-names></name><name><surname>Yoshida</surname><given-names>K.</given-names></name><name><surname>Miyagawa</surname><given-names>K.</given-names></name><name><surname>Asao</surname><given-names>Y.</given-names></name><name><surname>Takayama</surname><given-names>S.</given-names></name><name><surname>Nakashima</surname><given-names>S.</given-names></name><etal></etal></person-group> (<year>2007</year>). <article-title>Rotenoids and flavonoids with anti-invasion of HT1080, anti-proliferation of U937, and differentiation-inducing activityin HL-60 from <italic>Erycibe expansa.</italic> Bioorg</article-title>. <source>Med. Chem.</source><volume>15</volume>, <fpage>1539</fpage>–<lpage>1546</lpage>. <pub-id pub-id-type="doi">10.1016/j.bmc.2006.09.024</pub-id></mixed-citation></ref><ref id="B83"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mishra</surname><given-names>K.</given-names></name><name><surname>Ojha</surname><given-names>H.</given-names></name><name><surname>Chaudhury</surname><given-names>N. K.</given-names></name></person-group> (<year>2012</year>). <article-title>Estimation of antiradical properties of antioxidants using DPPH assay: a critical review and results</article-title>. <source>Food Chem.</source><volume>130</volume>, <fpage>1036</fpage>–<lpage>1043</lpage>. <pub-id pub-id-type="doi">10.1016/j.foodchem.2011.07.127</pub-id></mixed-citation></ref><ref id="B84"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mukai</surname><given-names>R.</given-names></name></person-group> (<year>2018</year>). <article-title>Prenylation enhances the biological activity of dietary flavonoids by altering their bioavailability</article-title>. <source>Biosci. Biotech. Bioch.</source><volume>82</volume>, <fpage>207</fpage>–<lpage>215</lpage>. <pub-id pub-id-type="doi">10.1080/09168451.2017.1415750</pub-id></mixed-citation></ref><ref id="B85"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mvondo</surname><given-names>M. A.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Tanee Fomum</surname><given-names>S.</given-names></name><name><surname>Wandji</surname><given-names>J.</given-names></name></person-group> (<year>2012</year>). <article-title>Effects of alpinumisoflavone and abyssinone V-4′-methyl ether derived from <italic>Erythrina lysistemon</italic> (Fabaceae) on the genital tract of ovariectomized female Wistar Rat</article-title>. <source>Phytother. Res.</source><volume>26</volume>, <fpage>1029</fpage>–<lpage>1036</lpage>. <pub-id pub-id-type="doi">10.1002/ptr.3685</pub-id><pub-id pub-id-type="pmid">22183714</pub-id></mixed-citation></ref><ref id="B86"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mvondo</surname><given-names>M. A.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Fomum</surname><given-names>S. T.</given-names></name><name><surname>Wandji</surname><given-names>J.</given-names></name><name><surname>Vollmer</surname><given-names>G.</given-names></name></person-group> (<year>2011</year>). <article-title>A postmenopause-like model of ovariectomized Wistar rats to identify active principles of <italic>Erythrina lysistemon</italic> (Fabaceae)</article-title>. <source>Fitoterapia</source><volume>82</volume>, <fpage>939</fpage>–<lpage>949</lpage>. <pub-id pub-id-type="doi">10.1016/j.fitote.2011.05.009</pub-id><pub-id pub-id-type="pmid">21635940</pub-id></mixed-citation></ref><ref id="B87"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mvondo</surname><given-names>M. A.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Kretzschmar</surname><given-names>G.</given-names></name><name><surname>Bader</surname><given-names>M. I.</given-names></name><name><surname>Fomum</surname><given-names>S. T.</given-names></name><name><surname>Wandji</surname><given-names>J.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Alpinumisoflavone and abyssinone V 4′-methylether derived from <italic>Erythrina lysistemon</italic> (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats</article-title>. <source>J. Pharm. Pharmacol.</source><volume>67</volume>, <fpage>990</fpage>–<lpage>996</lpage>. <pub-id pub-id-type="doi">10.1111/jphp.12386</pub-id><pub-id pub-id-type="pmid">25683903</pub-id></mixed-citation></ref><ref id="B88"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Na</surname><given-names>M. K.</given-names></name><name><surname>Jang</surname><given-names>J. P.</given-names></name><name><surname>Njamen</surname><given-names>D.</given-names></name><name><surname>Mbafor</surname><given-names>J. T.</given-names></name><name><surname>Fomum</surname><given-names>Z. T.</given-names></name><name><surname>Kim</surname><given-names>B. Y.</given-names></name><etal></etal></person-group> (<year>2006</year>). <article-title>Protein tyrosine phosphatase-1B inhibitory activity of isoprenylated flavonoids isolated from <italic>Erythrina mildbraedii</italic></article-title>. <source>J. Nat. Prod.</source><volume>69</volume>, <fpage>1572</fpage>–<lpage>1576</lpage>. <pub-id pub-id-type="doi">10.1021/np0601861</pub-id><pub-id pub-id-type="pmid">17125223</pub-id></mixed-citation></ref><ref id="B89"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Namkoong</surname><given-names>S.</given-names></name><name><surname>Kim</surname><given-names>T. J.</given-names></name><name><surname>Jang</surname><given-names>I. S.</given-names></name><name><surname>Kang</surname><given-names>K. W.</given-names></name><name><surname>Oh</surname><given-names>W. K.</given-names></name><name><surname>Park</surname><given-names>J.</given-names></name></person-group> (<year>2011</year>). <article-title>Alpinumisoflavone induces apoptosis and suppresses extracellular signal-regulated kinases/mitogen activated protein kinase and Nuclear Factor-κB pathways in lung tumor cells</article-title>. <source>Biol. Pharm. Bull.</source><volume>34</volume>, <fpage>203</fpage>–<lpage>208</lpage>. <pub-id pub-id-type="doi">10.1248/bpb.34.203</pub-id><pub-id pub-id-type="pmid">21415528</pub-id></mixed-citation></ref><ref id="B90"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Namouchi</surname><given-names>A.</given-names></name><name><surname>Cimino</surname><given-names>M.</given-names></name><name><surname>Favre-Rochex</surname><given-names>S.</given-names></name><name><surname>Charles</surname><given-names>P.</given-names></name><name><surname>Gicquel</surname><given-names>B.</given-names></name></person-group> (<year>2017</year>). <article-title>Phenotypic and genomic comparison of <italic>Mycobacterium aurum</italic> and surrogate model species to <italic>Mycobacterium tuberculosis</italic>: implications for drug discovery</article-title>. <source>BMC Genomics</source><volume>18</volume>, <fpage>530</fpage>. <pub-id pub-id-type="doi">10.1186/s12864-017-3924-y</pub-id><pub-id pub-id-type="pmid">28705154</pub-id></mixed-citation></ref><ref id="B91"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nana</surname><given-names>F.</given-names></name><name><surname>Sandjo</surname><given-names>L. S.</given-names></name><name><surname>Keumedjio</surname><given-names>F.</given-names></name><name><surname>Ambassa</surname><given-names>P.</given-names></name><name><surname>Malik</surname><given-names>R.</given-names></name><name><surname>Kuete</surname><given-names>V.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Ceramides and cytotoxic constituents from <italic>Ficus glumosa</italic> Del. (Moraceae)</article-title>. <source>J. Braz. Chem. Soc.</source><volume>23</volume>, <fpage>482</fpage>–<lpage>487</lpage>. <pub-id pub-id-type="doi">10.1590/S0103-50532012000300015</pub-id></mixed-citation></ref><ref id="B92"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Naoi</surname><given-names>M.</given-names></name><name><surname>Maruyama</surname><given-names>W.</given-names></name><name><surname>Shamoto-Nagai</surname><given-names>M.</given-names></name></person-group> (<year>2018</year>). <article-title>Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons</article-title>. <source>J. Neural Transm.</source><volume>125</volume>, <fpage>1635</fpage>–<lpage>1650</lpage>. <pub-id pub-id-type="doi">10.1007/s00702-017-1832-6</pub-id><pub-id pub-id-type="pmid">29279995</pub-id></mixed-citation></ref><ref id="B93"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ncube</surname><given-names>N. S.</given-names></name><name><surname>Afolayan</surname><given-names>A. J.</given-names></name><name><surname>Okoh</surname><given-names>A. I.</given-names></name></person-group> (<year>2008</year>). <article-title>Assessment techniques of antimicrobial properties of natural compounds of plant origin: current methods and future trends</article-title>. <source>Afr. J. Biotechnol.</source><volume>7</volume>, <fpage>1797</fpage>–<lpage>1806</lpage>. <pub-id pub-id-type="doi">10.5897/AJB07.613</pub-id></mixed-citation></ref><ref id="B94"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ndemangou</surname><given-names>B.</given-names></name><name><surname>Tedjon Sielinou</surname><given-names>V.</given-names></name><name><surname>Vardamides</surname><given-names>J. C.</given-names></name><name><surname>Shaiq Ali</surname><given-names>M.</given-names></name><name><surname>Lateef</surname><given-names>M.</given-names></name><name><surname>Iqbal</surname><given-names>L.</given-names></name><etal></etal></person-group> (<year>2013</year>). <article-title>Urease inhibitory isoflavonoids from different parts of <italic>Calopogonium mucunoides</italic> (Fabaceae)</article-title>. <source>J. Enzym. Inhib. Med. Chem.</source><volume>28</volume> (<issue>6</issue>), <fpage>1156</fpage>–<lpage>1161</lpage>. <pub-id pub-id-type="doi">10.3109/14756366.2012.719025</pub-id></mixed-citation></ref><ref id="B95"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nkengfack</surname><given-names>A. E.</given-names></name><name><surname>Azebaze</surname><given-names>A. G. B.</given-names></name><name><surname>Waffo</surname><given-names>A. K.</given-names></name><name><surname>Fomum</surname><given-names>Z. T.</given-names></name><name><surname>Meyer</surname><given-names>M.</given-names></name><name><surname>Van Heerden</surname><given-names>F. R.</given-names></name></person-group> (<year>2001</year>). <article-title>Cytotoxic isoflavones from <italic>Erythrina indica</italic></article-title>. <source>Phytochemistry</source><volume>58</volume>, <fpage>1113</fpage>–<lpage>1120</lpage>. <pub-id pub-id-type="doi">10.1016/S0031-9422(01)00368-5</pub-id><pub-id pub-id-type="pmid">11730876</pub-id></mixed-citation></ref><ref id="B96"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nwodo</surname><given-names>J. N.</given-names></name><name><surname>Ibezim</surname><given-names>A.</given-names></name><name><surname>Simoben</surname><given-names>C. V.</given-names></name><name><surname>Ntie-Kang</surname><given-names>F.</given-names></name></person-group> (<year>2016</year>). <article-title>Exploring cancer therapeutics with natural products from African medicinal plants, Part II: alkaloids, terpenoids and flavonoids</article-title>. <source>Anti-Cancer Agent. Med. Chem.</source><volume>16</volume>, <fpage>108</fpage>–<lpage>127</lpage>. <pub-id pub-id-type="doi">10.2174/1871520615666150520143827</pub-id></mixed-citation></ref><ref id="B97"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nyandoro</surname><given-names>S. S.</given-names></name><name><surname>Munissi</surname><given-names>J. J. E.</given-names></name><name><surname>Kombo</surname><given-names>M.</given-names></name><name><surname>Mgina</surname><given-names>C. A.</given-names></name><name><surname>Pan</surname><given-names>F.</given-names></name><name><surname>Gruhonjic</surname><given-names>A.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Flavonoids from <italic>Erythrina schliebenii</italic></article-title>. <source>J. Nat. Prod.</source><volume>80</volume>, <fpage>377</fpage>–<lpage>383</lpage>. <pub-id pub-id-type="doi">10.1021/acs.jnatprod.6b00839</pub-id><pub-id pub-id-type="pmid">28112509</pub-id></mixed-citation></ref><ref id="B98"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oakley</surname><given-names>R. H.</given-names></name><name><surname>Cidlowski</surname><given-names>J. A.</given-names></name></person-group> (<year>2013</year>). <article-title>The biology of the glucocorticoid receptor: new signaling mechanisms in health and disease</article-title>. <source>J. Allergy Clin. Immun.</source><volume>132</volume>, <fpage>1033</fpage>–<lpage>1044</lpage>. <pub-id pub-id-type="doi">10.1016/j.jaci.2013.09.007</pub-id><pub-id pub-id-type="pmid">24084075</pub-id></mixed-citation></ref><ref id="B99"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ocloo</surname><given-names>A.</given-names></name><name><surname>Kingsford-Adaboh</surname><given-names>R.</given-names></name><name><surname>Murray</surname><given-names>A. J.</given-names></name></person-group> (<year>2017</year>). <article-title>Inhibition of mitochondrial respiratory chain activity by O, O-dimethyl- and 4-O-methyl-Alpinumisoflavones</article-title>. <source>J. Appl. Pharm. Sci.</source><volume>7</volume>, <fpage>95</fpage>–<lpage>100</lpage>.</mixed-citation></ref><ref id="B100"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oh</surname><given-names>W. K.</given-names></name><name><surname>Lee</surname><given-names>C. H.</given-names></name><name><surname>Seo</surname><given-names>J. H.</given-names></name><name><surname>Chung</surname><given-names>M. Y.</given-names></name><name><surname>Cui</surname><given-names>L.</given-names></name><name><surname>Fomum</surname><given-names>Z. T.</given-names></name><etal></etal></person-group> (<year>2009</year>). <article-title>Diacylglycerol acyltransferase-inhibitory compounds from <italic>Erythrina senegalensis</italic></article-title>. <source>Arch. Pharm. Res.</source><volume>32</volume>, <fpage>43</fpage>–<lpage>47</lpage>. <pub-id pub-id-type="doi">10.1007/s12272-009-1116-2</pub-id><pub-id pub-id-type="pmid">19183875</pub-id></mixed-citation></ref><ref id="B101"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oh</surname><given-names>W. K.</given-names></name><name><surname>Kim</surname><given-names>B. Y.</given-names></name><name><surname>Oh</surname><given-names>H.</given-names></name><name><surname>Kim</surname><given-names>B. S.</given-names></name><name><surname>Ahn</surname><given-names>J. S.</given-names></name></person-group> (<year>2005</year>). <article-title>Phospholipase Cγ1 inhibitory activities of prenylated flavonoids isolated from <italic>Erythrina senegalensis</italic></article-title>. <source>Planta Med.</source><volume>71</volume>, <fpage>780</fpage>–<lpage>782</lpage>. <pub-id pub-id-type="doi">10.1055/s-2005-864183</pub-id><pub-id pub-id-type="pmid">16142647</pub-id></mixed-citation></ref><ref id="B102"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Okamoto</surname><given-names>Y.</given-names></name><name><surname>Suzuki</surname><given-names>A.</given-names></name><name><surname>Ueda</surname><given-names>K.</given-names></name><name><surname>Ito</surname><given-names>C.</given-names></name><name><surname>Itoigawa</surname><given-names>M.</given-names></name><name><surname>Furukawa</surname><given-names>H.</given-names></name><etal></etal></person-group> (<year>2006</year>). <article-title>Anti-estrogenic activity of prenylated isoflavones from <italic>Millettia pachycarpa</italic>: implications for pharmacophores and unique mechanisms</article-title>. <source>J. Health Sci.</source><volume>52</volume> (<issue>2</issue>), <fpage>186</fpage>–<lpage>191</lpage>. <pub-id pub-id-type="doi">10.1248/jhs.52.186</pub-id></mixed-citation></ref><ref id="B103"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patil</surname><given-names>V. M.</given-names></name><name><surname>Masand</surname><given-names>N.</given-names></name></person-group> (<year>2019</year>). <article-title>Anticancer potential of flavonoids: chemistry, biological activities, and future perspectives</article-title>. <source>Stud. Nat. Prod. Chem.</source><volume>59</volume>, <fpage>401</fpage>–<lpage>430</lpage>. <pub-id pub-id-type="doi">10.1016/B978-0-444-64179-3.00012-8</pub-id></mixed-citation></ref><ref id="B104"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Perese</surname><given-names>D. A.</given-names></name><name><surname>Ulman</surname><given-names>J.</given-names></name><name><surname>Viola</surname><given-names>J.</given-names></name><name><surname>Ewing</surname><given-names>S. E. E.</given-names></name><name><surname>Bankiewicz</surname><given-names>K. S.</given-names></name></person-group> (<year>1989</year>). <article-title>A 6-Hydroxydopamine-induced selective parkinsonian rat model</article-title>. <source>Brain Res.</source><volume>494</volume>, <fpage>285</fpage>–<lpage>293</lpage>. <pub-id pub-id-type="doi">10.1016/0006-8993(89)90597-0</pub-id><pub-id pub-id-type="pmid">2528389</pub-id></mixed-citation></ref><ref id="B105"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Power</surname><given-names>O.</given-names></name><name><surname>Jakeman</surname><given-names>P.</given-names></name><name><surname>FitzGerald</surname><given-names>R. J.</given-names></name></person-group> (<year>2013</year>). <article-title>Antioxidative peptides: enzymatic production, <italic>in vitro</italic> and <italic>in vivo</italic> antioxidant activity and potential applications of milk-derived antioxidative peptides</article-title>. <source>Amino Acids</source><volume>44</volume>, <fpage>797</fpage>–<lpage>820</lpage>. <pub-id pub-id-type="doi">10.1007/s00726-012-1393-9</pub-id><pub-id pub-id-type="pmid">22968663</pub-id></mixed-citation></ref><ref id="B106"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prior</surname><given-names>R. L.</given-names></name><name><surname>Wu</surname><given-names>X.</given-names></name><name><surname>Schaich</surname><given-names>K.</given-names></name></person-group> (<year>2005</year>). <article-title>Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements</article-title>. <source>J. Agric. Food Chem.</source><volume>53</volume>, <fpage>4290</fpage>–<lpage>4302</lpage>. <pub-id pub-id-type="doi">10.1021/jf0502698</pub-id><pub-id pub-id-type="pmid">15884874</pub-id></mixed-citation></ref><ref id="B107"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rahman</surname><given-names>M. Z.</given-names></name><name><surname>Rahman</surname><given-names>M. S.</given-names></name><name><surname>Kaisar</surname><given-names>A.</given-names></name><name><surname>Hossain</surname><given-names>A.</given-names></name><name><surname>Rashid</surname><given-names>M. A.</given-names></name></person-group> (<year>2010</year>). <article-title>Bioactive isoflavones from <italic>Erythrina variegata</italic> L</article-title>. <source>Turk. J. Pharm. Sci.</source><volume>7</volume>, <fpage>21</fpage>–<lpage>28</lpage>.</mixed-citation></ref><ref id="B108"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rani</surname><given-names>K.</given-names></name></person-group> (<year>2017</year>). <article-title>Role of antioxidants in prevention of diseases</article-title>. <source>J. Appl. Biotechnol. Bioeng.</source><volume>4</volume> (<issue>1</issue>), <fpage>00091</fpage>. <pub-id pub-id-type="doi">10.15406/jabb.2017.04.00091</pub-id></mixed-citation></ref><ref id="B109"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reynaud</surname><given-names>J.</given-names></name><name><surname>Guilet</surname><given-names>D.</given-names></name><name><surname>Terreux</surname><given-names>R.</given-names></name><name><surname>Lussignol</surname><given-names>M.</given-names></name><name><surname>Walchshofer</surname><given-names>N.</given-names></name></person-group> (<year>2005</year>). <article-title>Isoflavonoids in non-leguminous families: an update</article-title>. <source>Nat. Prod. Rep.</source><volume>22</volume>, <fpage>504</fpage>–<lpage>515</lpage>. <pub-id pub-id-type="doi">10.1039/b416248j</pub-id><pub-id pub-id-type="pmid">16047048</pub-id></mixed-citation></ref><ref id="B110"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Riaz</surname><given-names>N.</given-names></name><name><surname>Akram Naveed</surname><given-names>M.</given-names></name><name><surname>Saleem</surname><given-names>M.</given-names></name><name><surname>Jabeen</surname><given-names>B.</given-names></name><name><surname>Ashraf</surname><given-names>M.</given-names></name><name><surname>Ejaz</surname><given-names>S. A.</given-names></name><etal></etal></person-group> (<year>2012</year>). <article-title>Cholinesterase inhibitory constituents from <italic>Ficus bengalensis</italic></article-title>. <source>J. Asian Nat. Prod. Res.</source><volume>14</volume>, <fpage>1149</fpage>–<lpage>1155</lpage>. <pub-id pub-id-type="doi">10.1080/10286020.2012.733702</pub-id><pub-id pub-id-type="pmid">23106601</pub-id></mixed-citation></ref><ref id="B111"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ríos</surname><given-names>J. L.</given-names></name><name><surname>Recio</surname><given-names>M. C.</given-names></name></person-group> (<year>2005</year>). <article-title>Medicinal plants and antimicrobial activity</article-title>. <source>J. Ethnopharmacol.</source><volume>100</volume>, <fpage>80</fpage>–<lpage>84</lpage>. <pub-id pub-id-type="doi">10.1016/j.jep.2005.04.025</pub-id><pub-id pub-id-type="pmid">15964727</pub-id></mixed-citation></ref><ref id="B112"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rohwer</surname><given-names>N.</given-names></name><name><surname>Cramer</surname><given-names>T.</given-names></name></person-group> (<year>2011</year>). <article-title>Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways</article-title>. <source>Drug Resist. Updat.</source><volume>14</volume>, <fpage>191</fpage>–<lpage>201</lpage>. <pub-id pub-id-type="doi">10.1016/j.drup.2011.03.001</pub-id><pub-id pub-id-type="pmid">21466972</pub-id></mixed-citation></ref><ref id="B113"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>San-Martín</surname><given-names>A.</given-names></name><name><surname>Donoso</surname><given-names>V.</given-names></name><name><surname>Leiva</surname><given-names>S.</given-names></name><name><surname>Bacho</surname><given-names>M.</given-names></name><name><surname>Núñez</surname><given-names>S.</given-names></name><name><surname>Gutierrez</surname><given-names>M.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Molecular docking studies of the antitumoral activity and characterization of new chalcone</article-title>. <source>Curr. Top. Med. Chem.</source><volume>15</volume>, <fpage>1743</fpage>–<lpage>1749</lpage>. <pub-id pub-id-type="doi">10.2174/1568026615666150427125033</pub-id><pub-id pub-id-type="pmid">25915607</pub-id></mixed-citation></ref><ref id="B114"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sathishkumar</surname><given-names>R.</given-names></name><name><surname>Tharani</surname><given-names>R.</given-names></name></person-group> (<year>2017</year>). <article-title><italic>In silico</italic> determination of efficiency of plant secondary metabolites to eradicate Trachoma-A blinding keratoconjuctivitis disease</article-title>. <source>J. Appl. Pharm. Sci.</source><volume>7</volume>, <fpage>116</fpage>–<lpage>121</lpage>.</mixed-citation></ref><ref id="B115"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schito</surname><given-names>L.</given-names></name><name><surname>Semenza</surname><given-names>G. L.</given-names></name></person-group> (<year>2016</year>). <article-title>Hypoxia-inducible factors: master regulators of cancer progression</article-title>. <source>Trends Cancer</source><volume>2</volume>, <fpage>758</fpage>–<lpage>770</lpage>. <pub-id pub-id-type="doi">10.1016/j.trecan.2016.10.016</pub-id><pub-id pub-id-type="pmid">28741521</pub-id></mixed-citation></ref><ref id="B116"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schober</surname><given-names>A.</given-names></name></person-group> (<year>2004</year>). <article-title>Classic toxin-induced animal models of Parkinson’s disease:6-OHDA and MPTP</article-title>. <source>Cell Tissue Res.</source><volume>318</volume>, <fpage>215</fpage>–<lpage>224</lpage>. <pub-id pub-id-type="doi">10.1007/s00441-004-0938-y</pub-id><pub-id pub-id-type="pmid">15503155</pub-id></mixed-citation></ref><ref id="B117"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sharma</surname><given-names>O. P.</given-names></name><name><surname>Bhat</surname><given-names>T. K.</given-names></name></person-group> (<year>2009</year>). <article-title>DPPH antioxidant assay revisited</article-title>. <source>Food Chem.</source><volume>113</volume>, <fpage>1202</fpage>–<lpage>1205</lpage>. <pub-id pub-id-type="doi">10.1016/j.foodchem.2008.08.008</pub-id></mixed-citation></ref><ref id="B118"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shen</surname><given-names>B.</given-names></name></person-group> (<year>2015</year>). <article-title>A new golden age of natural products drug discovery</article-title>. <source>Cell</source><volume>163</volume>, <fpage>1297</fpage>–<lpage>1300</lpage>. <pub-id pub-id-type="doi">10.1016/j.cell.2015.11.031</pub-id><pub-id pub-id-type="pmid">26638061</pub-id></mixed-citation></ref><ref id="B119"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sherif</surname><given-names>S. H.</given-names></name><name><surname>Vidavalur</surname><given-names>S.</given-names></name><name><surname>Muralidhar</surname><given-names>P.</given-names></name><name><surname>Murthy</surname><given-names>Y. L. N.</given-names></name></person-group> (<year>2015</year>). <article-title>Synthesis and antioxidant activities of naturally occurring alpinum isoflavone, 4′-O-methylalpinum isoflavone and their synthetic analogues</article-title>. <source>Der Pharma Chemica</source><volume>7</volume> (<issue>5</issue>), <fpage>116</fpage>–<lpage>123</lpage>.</mixed-citation></ref><ref id="B120"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>L.</given-names></name></person-group> (<year>2010</year>). <article-title>Separation, purification and structure characterization of a polysaccharide from root of <italic>Cudrania tricuspidata</italic></article-title>. <source>Asian J. Exp. Biol. Sci.</source><volume>1</volume>, <fpage>311</fpage>–<lpage>314</lpage>.</mixed-citation></ref><ref id="B121"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shin</surname><given-names>G. R.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Lee</surname><given-names>S.</given-names></name><name><surname>Do</surname><given-names>S. G.</given-names></name><name><surname>Shin</surname><given-names>E.</given-names></name><name><surname>Lee</surname><given-names>C. H.</given-names></name></person-group> (<year>2015</year>). <article-title>Maturity stage-specific metabolite profiling of <italic>Cudrania tricuspidata</italic> and its correlation with antioxidant activity</article-title>. <source>Ind. Crop. Prod.</source><volume>70</volume>, <fpage>322</fpage>–<lpage>331</lpage>. <pub-id pub-id-type="doi">10.1016/j.indcrop.2015.01.048</pub-id></mixed-citation></ref><ref id="B122"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Su</surname><given-names>Z. Q.</given-names></name><name><surname>Mo</surname><given-names>Z. Z.</given-names></name><name><surname>Liao</surname><given-names>J. B.</given-names></name><name><surname>Feng</surname><given-names>X. X.</given-names></name><name><surname>Liang</surname><given-names>Y. Z.</given-names></name><name><surname>Zhang</surname><given-names>X.</given-names></name><etal></etal></person-group> (<year>2014</year>). <article-title>Usnic acid protects LPS-induced acute lung injury in mice through attenuating inflammatory responses and oxidative stress</article-title>. <source>Int. Immunopharmacol.</source><volume>22</volume>, <fpage>371</fpage>–<lpage>378</lpage>. <pub-id pub-id-type="doi">10.1016/j.intimp.2014.06.043</pub-id><pub-id pub-id-type="pmid">25068825</pub-id></mixed-citation></ref><ref id="B123"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sudanich</surname><given-names>S.</given-names></name><name><surname>Tiyaworanant</surname><given-names>S.</given-names></name><name><surname>Yenjai</surname><given-names>C.</given-names></name></person-group> (<year>2017</year>). <article-title>Cytotoxicity of flavonoids and isoflavonoids from <italic>Crotalaria bracteata</italic></article-title>. <source>Nat. Prod. Res.</source><volume>31</volume>, <fpage>2641</fpage>–<lpage>2646</lpage>. <pub-id pub-id-type="doi">10.1080/14786419.2017.1289207</pub-id><pub-id pub-id-type="pmid">28278675</pub-id></mixed-citation></ref><ref id="B124"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>J. B. L.</given-names></name><name><surname>Lim</surname><given-names>Y. Y.</given-names></name></person-group> (<year>2015</year>). <article-title>Critical analysis of current methods for assessing the <italic>in vitro</italic> antioxidant and antibacterial activity of plant extracts</article-title>. <source>Food Chem.</source><volume>172</volume>, <fpage>814</fpage>–<lpage>822</lpage>. <pub-id pub-id-type="doi">10.1016/j.foodchem.2014.09.141</pub-id><pub-id pub-id-type="pmid">25442625</pub-id></mixed-citation></ref><ref id="B125"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>Y.</given-names></name></person-group> (<year>2014</year>). <article-title>Glucocorticoid and bone. Pathogenesis of glucocorticoid-induced osteoporosis</article-title>. <source>Clin. Calcium</source><volume>24</volume>, <fpage>1289</fpage>–<lpage>1294</lpage>.<pub-id pub-id-type="pmid">25177000</pub-id></mixed-citation></ref><ref id="B126"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tjahjandarie</surname><given-names>T. S.</given-names></name><name><surname>Tanjung</surname><given-names>M.</given-names></name></person-group> (<year>2015</year>a). <article-title>Phenolic compounds from the stem bark of <italic>Erythrina orientalis</italic> and their cytotoxic and antioxidant activities</article-title>. <source>Der Pharma Chemica</source><volume>7</volume> (<issue>1</issue>), <fpage>206</fpage>–<lpage>211</lpage>.</mixed-citation></ref><ref id="B127"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tjahjandarie</surname><given-names>T. S.</given-names></name><name><surname>Tanjung</surname><given-names>M.</given-names></name></person-group> (<year>2015</year>b). <article-title>Antiplasmodial isoprenylated flavonoids from the stem bark of <italic>Erythrina ovalifolia</italic> Roxb</article-title>. <source>Der Pharmacia Lettre</source><volume>7</volume> (<issue>2</issue>), <fpage>35</fpage>–<lpage>39</lpage>.</mixed-citation></ref><ref id="B128"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tong</surname><given-names>J.</given-names></name><name><surname>Rathitharan</surname><given-names>G.</given-names></name><name><surname>Meyer</surname><given-names>J. H.</given-names></name><name><surname>Furukawa</surname><given-names>Y.</given-names></name><name><surname>Ang</surname><given-names>L. C.</given-names></name><name><surname>Boileau</surname><given-names>I.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title>Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency disorders</article-title>. <source>Brain</source><volume>140</volume>, <fpage>2460</fpage>–<lpage>2474</lpage>. <pub-id pub-id-type="doi">10.1093/brain/awx172</pub-id><pub-id pub-id-type="pmid">29050386</pub-id></mixed-citation></ref><ref id="B129"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Trinh</surname><given-names>B. T. D.</given-names></name><name><surname>Jäger</surname><given-names>A. K.</given-names></name><name><surname>Staerk</surname><given-names>D.</given-names></name></person-group> (<year>2017</year>). <article-title>High-resolution inhibition profiling combined with HPLC-HRMS-SPE-NMR for identification of PTP1B inhibitors from Vietnamese Plants</article-title>. <source>Molecules</source><volume>22</volume>, <fpage>1228</fpage>. <pub-id pub-id-type="doi">10.3390/molecules22071228</pub-id></mixed-citation></ref><ref id="B130"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uddin</surname><given-names>M. M. N.</given-names></name><name><surname>Emran</surname><given-names>T. B.</given-names></name><name><surname>Mahib</surname><given-names>M. M. R.</given-names></name><name><surname>Dash</surname><given-names>R.</given-names></name></person-group> (<year>2014</year>). <article-title>Molecular docking and analgesic studies of <italic>Erythrina variegata</italic>‘s derived phytochemicals with COX enzymes</article-title>. <source>Bioinformation</source><volume>10</volume> (<issue>10</issue>), <fpage>630</fpage>–<lpage>636</lpage>. <pub-id pub-id-type="doi">10.6026/97320630010630</pub-id><pub-id pub-id-type="pmid">25489172</pub-id></mixed-citation></ref><ref id="B131"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van de Laar</surname><given-names>F. A.</given-names></name><name><surname>Lucassen</surname><given-names>P. L.</given-names></name><name><surname>Akkermans</surname><given-names>R. P.</given-names></name><name><surname>de Lisdonk</surname><given-names>E. H.</given-names></name><name><surname>Rutten</surname><given-names>G. E.</given-names></name><name><surname>Van Weel</surname><given-names>C.</given-names></name></person-group> (<year>2005</year>). <article-title>Glucosidase inhibitors for patients with type 2 diabetes</article-title>. <source>Diabetes Care</source><volume>28</volume>, <fpage>166</fpage>–<lpage>175</lpage>. <pub-id pub-id-type="doi">10.2337/diacare.28.7.1841</pub-id></mixed-citation></ref><ref id="B132"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Tonder</surname><given-names>A.</given-names></name><name><surname>Joubert</surname><given-names>A. M.</given-names></name><name><surname>Cromarty</surname><given-names>A. D.</given-names></name></person-group> (<year>2015</year>). <article-title>Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays</article-title>. <source>BMC Research Notes</source><volume>8</volume>, <fpage>47</fpage>. <pub-id pub-id-type="doi">10.1186/s13104-015-1000-8</pub-id><pub-id pub-id-type="pmid">25884200</pub-id></mixed-citation></ref><ref id="B133"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Venturelli</surname><given-names>S.</given-names></name><name><surname>Burkard</surname><given-names>M.</given-names></name><name><surname>Biendl</surname><given-names>M.</given-names></name><name><surname>Lauer</surname><given-names>U. M.</given-names></name><name><surname>Frank</surname><given-names>J.</given-names></name><name><surname>Busch</surname><given-names>C.</given-names></name></person-group> (<year>2016</year>). <article-title>Prenylated chalcones and flavonoids for the prevention and treatment of cancer</article-title>. <source>Nutrition</source><volume>32</volume>, <fpage>1171</fpage>–<lpage>1178</lpage>. <pub-id pub-id-type="doi">10.1016/j.nut.2016.03.020</pub-id><pub-id pub-id-type="pmid">27238957</pub-id></mixed-citation></ref><ref id="B134"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Waffo</surname><given-names>A. K.</given-names></name><name><surname>Azebaze</surname><given-names>G. A.</given-names></name><name><surname>Nkengfack</surname><given-names>A. E.</given-names></name><name><surname>Fomum</surname><given-names>Z. T.</given-names></name><name><surname>Meyer</surname><given-names>M.</given-names></name><name><surname>Bodo</surname><given-names>B.</given-names></name><etal></etal></person-group> (<year>2000</year>). <article-title>Indicanines B and C, two isoflavonoid derivatives from the root bark of <italic>Erythrina indica</italic></article-title>. <source>Phytochemistry</source><volume>53</volume>, <fpage>981</fpage>–<lpage>985</lpage>. <pub-id pub-id-type="doi">10.1016/S0031-9422(99)00615-9</pub-id><pub-id pub-id-type="pmid">10820816</pub-id></mixed-citation></ref><ref id="B135"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walle</surname><given-names>T.</given-names></name><name><surname>Ta</surname><given-names>N.</given-names></name><name><surname>Kawamori</surname><given-names>T.</given-names></name><name><surname>Wen</surname><given-names>X.</given-names></name><name><surname>Tsuji</surname><given-names>P. A.</given-names></name><name><surname>Walle</surname><given-names>U. K.</given-names></name></person-group> (<year>2007</year>). <article-title>Cancer chemopreventive properties of orally bioavailable flavonoids-methylated versus unmethylated flavones</article-title>. <source>Biochem. Pharmacol.</source><volume>73</volume>, <fpage>1288</fpage>–<lpage>1296</lpage>. <pub-id pub-id-type="doi">10.1016/j.bcp.2006.12.028</pub-id><pub-id pub-id-type="pmid">17250812</pub-id></mixed-citation></ref><ref id="B136"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>L. J.</given-names></name><name><surname>Jiang</surname><given-names>B.</given-names></name><name><surname>Wu</surname><given-names>N.</given-names></name><name><surname>Wang</surname><given-names>S. Y.</given-names></name><name><surname>Shi</surname><given-names>D. Y.</given-names></name></person-group> (<year>2015</year>). <article-title>Natural and semisynthetic protein tyrosine phosphatase 1B (PTP1B) inhibitors as anti-diabetic agents</article-title>. <source>RSC Adv.</source><volume>5</volume>, <fpage>48822</fpage>–<lpage>48834</lpage>. <pub-id pub-id-type="doi">10.1039/C5RA01754H</pub-id></mixed-citation></ref><ref id="B137"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>S. Y.</given-names></name><name><surname>Sun</surname><given-names>Z. L.</given-names></name><name><surname>Liu</surname><given-names>T.</given-names></name><name><surname>Gibbons</surname><given-names>S.</given-names></name><name><surname>Zhang</surname><given-names>W. J.</given-names></name><name><surname>Qing</surname><given-names>M.</given-names></name></person-group> (<year>2014</year>). <article-title>Flavonoids from <italic>Sophora moorcroftiana</italic> and their synergistic antibacterial effects on MRSA</article-title>. <source>Phytother. Res.</source><volume>28</volume>, <fpage>1071</fpage>–<lpage>1076</lpage>. <pub-id pub-id-type="doi">10.1002/ptr.5098</pub-id><pub-id pub-id-type="pmid">24338874</pub-id></mixed-citation></ref><ref id="B138"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>T.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Chu</surname><given-names>L.</given-names></name><name><surname>Wu</surname><given-names>T.</given-names></name><name><surname>You</surname><given-names>J.</given-names></name></person-group> (<year>2017</year>a). <article-title>Alpinumisoflavone suppresses tumour growth and metastasis of clear-cell renal cell carcinoma</article-title>. <source>Am. J. Cancer Res.</source><volume>7</volume>, <fpage>999</fpage>–<lpage>1015</lpage>.<pub-id pub-id-type="pmid">28469971</pub-id></mixed-citation></ref><ref id="B139"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Liu</surname><given-names>J.</given-names></name><name><surname>Pang</surname><given-names>Q.</given-names></name><name><surname>Tao</surname><given-names>D.</given-names></name></person-group> (<year>2017</year>b). <article-title>Alpinumisoflavone protects against glucocorticoid-induced osteoporosis through suppressing the apoptosis of osteoblastic and osteocytic cells</article-title>. <source>Biomed. Pharmacother.</source><volume>96</volume>, <fpage>993</fpage>–<lpage>999</lpage>. <pub-id pub-id-type="doi">10.1016/j.biopha.2017.11.136</pub-id><pub-id pub-id-type="pmid">29203387</pub-id></mixed-citation></ref><ref id="B140"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>T.</given-names></name><name><surname>Liu</surname><given-names>Y.</given-names></name><name><surname>Li</surname><given-names>X.</given-names></name><name><surname>Xu</surname><given-names>Q.</given-names></name><name><surname>Feng</surname><given-names>Y.</given-names></name><name><surname>Yang</surname><given-names>S.</given-names></name></person-group> (<year>2018</year>). <article-title>Isoflavones from green vegetable soya beans and their antimicrobial and antioxidant activities</article-title>. <source>J. Sci. Food Agric.</source><volume>98</volume>, <fpage>2043</fpage>–<lpage>2047</lpage>. <pub-id pub-id-type="doi">10.1002/jsfa.8663</pub-id><pub-id pub-id-type="pmid">28885710</pub-id></mixed-citation></ref><ref id="B141"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>P.</given-names></name><name><surname>Henning</surname><given-names>S. M.</given-names></name><name><surname>Heber</surname><given-names>D.</given-names></name></person-group> (<year>2010</year>). <article-title>Limitations of MTT and MTS-based assays for measurements of antiproliferative activity of green tea polyphenols</article-title>. <source>PLoS One</source><volume>5</volume> (<issue>4</issue>), <elocation-id>e10202</elocation-id>. <pub-id pub-id-type="doi">10.1371/journal.pone.0010202</pub-id><pub-id pub-id-type="pmid">20419137</pub-id></mixed-citation></ref><ref id="B142"><mixed-citation publication-type="book"><person-group person-group-type="author"><collab>WHO</collab></person-group> (<year>2017</year>). <source>Global Tuberculosis Report 2017</source>. <publisher-loc>Geneva</publisher-loc>: <publisher-name>World Health Organization</publisher-name>.</mixed-citation></ref><ref id="B143"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xin</surname><given-names>L. T.</given-names></name><name><surname>Yue</surname><given-names>S. J.</given-names></name><name><surname>Fan</surname><given-names>Y. C.</given-names></name><name><surname>Wu</surname><given-names>J. S.</given-names></name><name><surname>Yan</surname><given-names>D.</given-names></name><name><surname>Guan</surname><given-names>H. S.</given-names></name><etal></etal></person-group> (<year>2017</year>). <article-title><italic>Cudrania tricuspidata</italic>: an updated review on ethnomedicine, phytochemistry and pharmacology</article-title>. <source>RSC Adv.</source><volume>7</volume>, <fpage>31807</fpage>–<lpage>31832</lpage>. <pub-id pub-id-type="doi">10.1039/C7RA04322H</pub-id></mixed-citation></ref><ref id="B144"><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>Xiong</surname><given-names>W. Y.</given-names></name><name><surname>Wang</surname><given-names>J. Z.</given-names></name><name><surname>Shi</surname><given-names>T. D.</given-names></name></person-group>, (<year>1993</year>). <source>Woody medicine plants of China</source>. <publisher-loc>Shanghai</publisher-loc>: <publisher-name>Shanghai Science and Education Press</publisher-name>, Shanghai, <fpage>85</fpage>–<lpage>88</lpage>.</mixed-citation></ref><ref id="B145"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>X.</given-names></name><name><surname>Jiang</surname><given-names>Y.</given-names></name><name><surname>Yang</surname><given-names>J.</given-names></name><name><surname>He</surname><given-names>J.</given-names></name><name><surname>Sun</surname><given-names>J.</given-names></name><name><surname>Chen</surname><given-names>F.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>Prenylated flavonoids, promising nutraceuticals with impressive biological activities</article-title>. <source>Trends Food Sci. Tech.</source><volume>44</volume>, <fpage>93</fpage>–<lpage>104</lpage>. <pub-id pub-id-type="doi">10.1016/j.tifs.2015.03.007</pub-id></mixed-citation></ref><ref id="B146"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yeh</surname><given-names>C. H.</given-names></name><name><surname>Yang</surname><given-names>J. J.</given-names></name><name><surname>Yang</surname><given-names>M. L.</given-names></name><name><surname>Li</surname><given-names>Y. C.</given-names></name><name><surname>Kuan</surname><given-names>Y. H.</given-names></name></person-group> (<year>2014</year>). <article-title>Rutin decreases lipopolysaccharide-induced acute lung injury <italic>via</italic> inhibition of oxidative stress and the MAPK-NF-k B pathway</article-title>. <source>Free Radical Biol. Med.</source><volume>69</volume>, <fpage>249</fpage>–<lpage>257</lpage>. <pub-id pub-id-type="doi">10.1016/j.freeradbiomed.2014.01.028</pub-id><pub-id pub-id-type="pmid">24486341</pub-id></mixed-citation></ref><ref id="B147"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yin</surname><given-names>J.</given-names></name><name><surname>Han</surname><given-names>L.</given-names></name><name><surname>Cong</surname><given-names>W.</given-names></name></person-group> (<year>2018</year>). <article-title>Alpinumisoflavone rescues glucocorticoid-induced apoptosis of osteocytes <italic>via</italic> suppressing Nox2-dependent ROS generation</article-title>. <source>Pharmacol. Rep.</source><volume>70</volume>, <fpage>270</fpage>–<lpage>276</lpage>. <pub-id pub-id-type="doi">10.1016/j.pharep.2017.11.001</pub-id><pub-id pub-id-type="pmid">29477034</pub-id></mixed-citation></ref><ref id="B148"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>B.</given-names></name><name><surname>Fan</surname><given-names>X.</given-names></name><name><surname>Wang</surname><given-names>Z.</given-names></name><name><surname>Zhu</surname><given-names>W.</given-names></name><name><surname>Li</surname><given-names>J.</given-names></name></person-group> (<year>2017</year>). <article-title>Alpinumisoflavone radiosensitizes esophageal squamous cell carcinoma through inducing apoptosis and cell cycle arrest</article-title>. <source>Biomed. Pharmacother.</source><volume>95</volume>, <fpage>199</fpage>–<lpage>206</lpage>. <pub-id pub-id-type="doi">10.1016/j.biopha.2017.08.048</pub-id><pub-id pub-id-type="pmid">28843908</pub-id></mixed-citation></ref><ref id="B149"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>M.</given-names></name><name><surname>Qiu</surname><given-names>Q.</given-names></name><name><surname>Li</surname><given-names>Z.</given-names></name><name><surname>Sachdeva</surname><given-names>M.</given-names></name><name><surname>Min</surname><given-names>H.</given-names></name><name><surname>Cardona</surname><given-names>D. M.</given-names></name><etal></etal></person-group> (<year>2015</year>). <article-title>HIF-1α regulates the response of primary sarcomas to radiation therapy through a cell autonomous mechanism</article-title>. <source>Radiat. Res.</source><volume>183</volume>, <fpage>594</fpage>–<lpage>609</lpage>. <pub-id pub-id-type="doi">10.1667/RR14016.1</pub-id><pub-id pub-id-type="pmid">25973951</pub-id></mixed-citation></ref><ref id="B150"><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zheng</surname><given-names>Z. P.</given-names></name><name><surname>Tan</surname><given-names>H. Y.</given-names></name><name><surname>Chen</surname><given-names>J.</given-names></name><name><surname>Wang</surname><given-names>M.</given-names></name></person-group> (<year>2013</year>). <article-title>Characterization of tyrosinase inhibitors in the twigs of <italic>Cudrania tricuspidata</italic> and their structure–activity relationship study</article-title>. <source>Fitoterapia</source><volume>84</volume>, <fpage>242</fpage>–<lpage>247</lpage>. <pub-id pub-id-type="doi">10.1016/j.fitote.2012.12.006</pub-id><pub-id pub-id-type="pmid">23262271</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/ChloroquineV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000994 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000994 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= ChloroquineV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:6746831
|texte= A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:31551770" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a ChloroquineV1
| This area was generated with Dilib version V0.6.33. |  |