Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Pomegranate Fruit as a Rich Source of Biologically Active Compounds</title><author><name sortKey="Sreekumar, Sreeja" sort="Sreekumar, Sreeja" uniqKey="Sreekumar S" first="Sreeja" last="Sreekumar">Sreeja Sreekumar</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Sithul, Hima" sort="Sithul, Hima" uniqKey="Sithul H" first="Hima" last="Sithul">Hima Sithul</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Muraleedharan, Parvathy" sort="Muraleedharan, Parvathy" uniqKey="Muraleedharan P" first="Parvathy" last="Muraleedharan">Parvathy Muraleedharan</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Azeez, Juberiya Mohammed" sort="Azeez, Juberiya Mohammed" uniqKey="Azeez J" first="Juberiya Mohammed" last="Azeez">Juberiya Mohammed Azeez</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Sreeharshan, Sreeja" sort="Sreeharshan, Sreeja" uniqKey="Sreeharshan S" first="Sreeja" last="Sreeharshan">Sreeja Sreeharshan</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24818149</idno><idno type="pmc">4000966</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000966</idno><idno type="RBID">PMC:4000966</idno><idno type="doi">10.1155/2014/686921</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001351</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Pomegranate Fruit as a Rich Source of Biologically Active Compounds</title><author><name sortKey="Sreekumar, Sreeja" sort="Sreekumar, Sreeja" uniqKey="Sreekumar S" first="Sreeja" last="Sreekumar">Sreeja Sreekumar</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Sithul, Hima" sort="Sithul, Hima" uniqKey="Sithul H" first="Hima" last="Sithul">Hima Sithul</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Muraleedharan, Parvathy" sort="Muraleedharan, Parvathy" uniqKey="Muraleedharan P" first="Parvathy" last="Muraleedharan">Parvathy Muraleedharan</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Azeez, Juberiya Mohammed" sort="Azeez, Juberiya Mohammed" uniqKey="Azeez J" first="Juberiya Mohammed" last="Azeez">Juberiya Mohammed Azeez</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author><author><name sortKey="Sreeharshan, Sreeja" sort="Sreeharshan, Sreeja" uniqKey="Sreeharshan S" first="Sreeja" last="Sreeharshan">Sreeja Sreeharshan</name><affiliation><nlm:aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</nlm:aff></affiliation></author></analytic><series><title level="j">BioMed Research International</title><idno type="ISSN">2314-6133</idno><idno type="eISSN">2314-6141</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on <italic>Punica</italic>. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20–320 <italic><italic>μ</italic></italic>g/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17<italic><italic>β</italic></italic>-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells.
The results indicated that PME (80 <italic><italic>μ</italic></italic>g/mL) significantly increased ALP
(Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation.
The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model.
The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds. </p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Miguel, Mg" uniqKey="Miguel M">MG Miguel</name></author><author><name sortKey="Neves, Ma" uniqKey="Neves M">MA Neves</name></author><author><name sortKey="Antunes, Md" uniqKey="Antunes M">MD Antunes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elghamry, Mi" uniqKey="Elghamry M">MI Elghamry</name></author><author><name sortKey="Shihata, Im" uniqKey="Shihata I">IM Shihata</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Magee, Pj" uniqKey="Magee P">PJ Magee</name></author><author><name sortKey="Rowland, Ir" uniqKey="Rowland I">IR Rowland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barnes, S" uniqKey="Barnes S">S Barnes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adlercreutz, H" uniqKey="Adlercreutz H">H Adlercreutz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Glazier, Mg" uniqKey="Glazier M">MG Glazier</name></author><author><name sortKey="Bowman, Ma" uniqKey="Bowman M">MA Bowman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brzezinski, A" uniqKey="Brzezinski A">A Brzezinski</name></author><author><name sortKey="Debi, A" uniqKey="Debi A">A Debi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Halbreich, U" uniqKey="Halbreich U">U Halbreich</name></author><author><name sortKey="Kahn, Ls" uniqKey="Kahn L">LS Kahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hol, T" uniqKey="Hol T">T Hol</name></author><author><name sortKey="Cox, Mb" uniqKey="Cox M">MB Cox</name></author><author><name sortKey="Bryant, Hu" uniqKey="Bryant H">HU Bryant</name></author><author><name sortKey="Draper, Mw" uniqKey="Draper M">MW Draper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sierens, J" uniqKey="Sierens J">J Sierens</name></author><author><name sortKey="Hartley, Ja" uniqKey="Hartley J">JA Hartley</name></author><author><name sortKey="Campbell, Mj" uniqKey="Campbell M">MJ Campbell</name></author><author><name sortKey="Leathem, Ajc" uniqKey="Leathem A">AJC Leathem</name></author><author><name sortKey="Woodside, Jv" uniqKey="Woodside J">JV Woodside</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fadavi, A" uniqKey="Fadavi A">A Fadavi</name></author><author><name sortKey="Barzegar, M" uniqKey="Barzegar M">M Barzegar</name></author><author><name sortKey="Azizi, Mh" uniqKey="Azizi M">MH Azizi</name></author><author><name sortKey="Bayat, M" uniqKey="Bayat M">M Bayat</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Viuda Martos, M" uniqKey="Viuda Martos M">M Viuda-Martos</name></author><author><name sortKey="Fernandez L Aez, J" uniqKey="Fernandez L Aez J">J Fernández-Lóaez</name></author><author><name sortKey="Perez Lvarez, Ja" uniqKey="Perez Lvarez J">JA Pérez-álvarez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elfalleh, W" uniqKey="Elfalleh W">W Elfalleh</name></author><author><name sortKey="Hannachi, H" uniqKey="Hannachi H">H Hannachi</name></author><author><name sortKey="Tlili, N" uniqKey="Tlili N">N Tlili</name></author><author><name sortKey="Yahia, Y" uniqKey="Yahia Y">Y Yahia</name></author><author><name sortKey="Nasri, N" uniqKey="Nasri N">N Nasri</name></author><author><name sortKey="Ferchichi, A" uniqKey="Ferchichi A">A Ferchichi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kohno, H" uniqKey="Kohno H">H Kohno</name></author><author><name sortKey="Suzuki, R" uniqKey="Suzuki R">R Suzuki</name></author><author><name sortKey="Yasui, Y" uniqKey="Yasui Y">Y Yasui</name></author><author><name sortKey="Hosokawa, M" uniqKey="Hosokawa M">M Hosokawa</name></author><author><name sortKey="Miyashita, K" uniqKey="Miyashita K">K Miyashita</name></author><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T Tanaka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lansky, Ep" uniqKey="Lansky E">EP Lansky</name></author><author><name sortKey="Newman, Ra" uniqKey="Newman R">RA Newman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Monica, V" uniqKey="Monica V">V Monica</name></author><author><name sortKey="Raquel L Pinyi, H" uniqKey="Raquel L Pinyi H">H Raquel L Pinyi</name></author><author><name sortKey="Josep, Br" uniqKey="Josep B">BR Josep</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elfalleh, W" uniqKey="Elfalleh W">W Elfalleh</name></author><author><name sortKey="Tlili, N" uniqKey="Tlili N">N Tlili</name></author><author><name sortKey="Nasri, N" uniqKey="Nasri N">N Nasri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jain, S" uniqKey="Jain S">S Jain</name></author><author><name sortKey="Rai, R" uniqKey="Rai R">R Rai</name></author><author><name sortKey="Upadhyaya, Ar" uniqKey="Upadhyaya A">AR Upadhyaya</name></author><author><name sortKey="Malhotra, G" uniqKey="Malhotra G">G Malhotra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seeram, Np" uniqKey="Seeram N">NP Seeram</name></author><author><name sortKey="Nair, Mg" uniqKey="Nair M">MG Nair</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amakura, Y" uniqKey="Amakura Y">Y Amakura</name></author><author><name sortKey="Okada, M" uniqKey="Okada M">M Okada</name></author><author><name sortKey="Tsuji, S" uniqKey="Tsuji S">S Tsuji</name></author><author><name sortKey="Tonogai, Y" uniqKey="Tonogai Y">Y Tonogai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tanaka, T" uniqKey="Tanaka T">T Tanaka</name></author><author><name sortKey="Nonaka, G I" uniqKey="Nonaka G">G-I Nonaka</name></author><author><name sortKey="Nishioka, I" uniqKey="Nishioka I">I Nishioka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gil, Mi" uniqKey="Gil M">MI Gil</name></author><author><name sortKey="Tomas Barberan, Fa" uniqKey="Tomas Barberan F">FA Tomas-Barberan</name></author><author><name sortKey="Hess Pierce, B" uniqKey="Hess Pierce B">B Hess-Pierce</name></author><author><name sortKey="Holcroft, Dm" uniqKey="Holcroft D">DM Holcroft</name></author><author><name sortKey="Kader, Aa" uniqKey="Kader A">AA Kader</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neuhofer, H" uniqKey="Neuhofer H">H Neuhofer</name></author><author><name sortKey="Witte, L" uniqKey="Witte L">L Witte</name></author><author><name sortKey="Gorunovic, M" uniqKey="Gorunovic M">M Gorunovic</name></author><author><name sortKey="Czygan, F C" uniqKey="Czygan F">F-C Czygan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vidal, A" uniqKey="Vidal A">A Vidal</name></author><author><name sortKey="Fallarero, A" uniqKey="Fallarero A">A Fallarero</name></author><author><name sortKey="Pe A, Br" uniqKey="Pe A B">BR Peña</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Elswijk, Da" uniqKey="Van Elswijk D">DA van Elswijk</name></author><author><name sortKey="Schobel, Up" uniqKey="Schobel U">UP Schobel</name></author><author><name sortKey="Lansky, Ep" uniqKey="Lansky E">EP Lansky</name></author><author><name sortKey="Irth, H" uniqKey="Irth H">H Irth</name></author><author><name sortKey="Van Der Greef, J" uniqKey="Van Der Greef J">J van der Greef</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Artik, N" uniqKey="Artik N">N Artik</name></author><author><name sortKey="Ceremroglu, B" uniqKey="Ceremroglu B">B Ceremroglu</name></author><author><name sortKey="Murakami, H" uniqKey="Murakami H">H Murakami</name></author><author><name sortKey="Mori, T" uniqKey="Mori T">T Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cui, S M" uniqKey="Cui S">S-M Cui</name></author><author><name sortKey="Sasada, Y" uniqKey="Sasada Y">Y Sasada</name></author><author><name sortKey="Sato, H" uniqKey="Sato H">H Sato</name></author><author><name sortKey="Nii, N" uniqKey="Nii N">N Nii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Poyrazo Lu, E" uniqKey="Poyrazo Lu E">E Poyrazoğlu</name></author><author><name sortKey="Gokmen, V" uniqKey="Gokmen V">V Gökmen</name></author><author><name sortKey="Artik, N" uniqKey="Artik N">N Artik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Du, Ct" uniqKey="Du C">CT Du</name></author><author><name sortKey="Wang, Pl" uniqKey="Wang P">PL Wang</name></author><author><name sortKey="Francis, Fj" uniqKey="Francis F">FJ Francis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waheed, S" uniqKey="Waheed S">S Waheed</name></author><author><name sortKey="Siddique, N" uniqKey="Siddique N">N Siddique</name></author><author><name sortKey="Rahman, A" uniqKey="Rahman A">A Rahman</name></author><author><name sortKey="Zaidi, Jh" uniqKey="Zaidi J">JH Zaidi</name></author><author><name sortKey="Ahmad, S" uniqKey="Ahmad S">S Ahmad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Thw" uniqKey="Huang T">THW Huang</name></author><author><name sortKey="Peng, G" uniqKey="Peng G">G Peng</name></author><author><name sortKey="Kota, Bp" uniqKey="Kota B">BP Kota</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Batta, Ak" uniqKey="Batta A">AK Batta</name></author><author><name sortKey="Rangaswami, S" uniqKey="Rangaswami S">S Rangaswami</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lan, J" uniqKey="Lan J">J Lan</name></author><author><name sortKey="Lei, F" uniqKey="Lei F">F Lei</name></author><author><name sortKey="Hua, L" uniqKey="Hua L">L Hua</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Xing, D" uniqKey="Xing D">D Xing</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chaitra, Rh" uniqKey="Chaitra R">RH Chaitra</name></author><author><name sortKey="Madhuri, M" uniqKey="Madhuri M">M Madhuri</name></author><author><name sortKey="Swaroop, T" uniqKey="Swaroop T">T Swaroop</name></author><author><name sortKey="Arijit, D" uniqKey="Arijit D">D Arijit</name></author><author><name sortKey="Sourav, B" uniqKey="Sourav B">B Sourav</name></author><author><name sortKey="Rohit, Kc" uniqKey="Rohit K">KC Rohit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nawwar, Mam" uniqKey="Nawwar M">MAM Nawwar</name></author><author><name sortKey="Hussein, Sam" uniqKey="Hussein S">SAM Hussein</name></author><author><name sortKey="Merfort, I" uniqKey="Merfort I">I Merfort</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, R F" uniqKey="Wang R">R-F Wang</name></author><author><name sortKey="Xie, W D" uniqKey="Xie W">W-D Xie</name></author><author><name sortKey="Zhang, Z" uniqKey="Zhang Z">Z Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schubert, Sy" uniqKey="Schubert S">SY Schubert</name></author><author><name sortKey="Lansky, Ep" uniqKey="Lansky E">EP Lansky</name></author><author><name sortKey="Neeman, I" uniqKey="Neeman I">I Neeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hornung, E" uniqKey="Hornung E">E Hornung</name></author><author><name sortKey="Pernstich, C" uniqKey="Pernstich C">C Pernstich</name></author><author><name sortKey="Feussner, I" uniqKey="Feussner I">I Feussner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abd El Wahab, Sm" uniqKey="Abd El Wahab S">SM Abd El Wahab</name></author><author><name sortKey="El Fiki, Nm" uniqKey="El Fiki N">NM El Fiki</name></author><author><name sortKey="Mostafa, Sf" uniqKey="Mostafa S">SF Mostafa</name></author><author><name sortKey="Hassan, Aeb" uniqKey="Hassan A">AEB Hassan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Nd" uniqKey="Kim N">ND Kim</name></author><author><name sortKey="Mehta, R" uniqKey="Mehta R">R Mehta</name></author><author><name sortKey="Yu, W" uniqKey="Yu W">W Yu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lansky, Ep" uniqKey="Lansky E">EP Lansky</name></author><author><name sortKey="Jiang, W" uniqKey="Jiang W">W Jiang</name></author><author><name sortKey="Mo, H" uniqKey="Mo H">H Mo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurenka, J" uniqKey="Jurenka J">J Jurenka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neurath, Ar" uniqKey="Neurath A">AR Neurath</name></author><author><name sortKey="Strick, N" uniqKey="Strick N">N Strick</name></author><author><name sortKey="Li, Y Y" uniqKey="Li Y">Y-Y Li</name></author><author><name sortKey="Debnath, Ak" uniqKey="Debnath A">AK Debnath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toi, M" uniqKey="Toi M">M Toi</name></author><author><name sortKey="Bando, H" uniqKey="Bando H">H Bando</name></author><author><name sortKey="Ramachandran, C" uniqKey="Ramachandran C">C Ramachandran</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehta, R" uniqKey="Mehta R">R Mehta</name></author><author><name sortKey="Lansky, Ep" uniqKey="Lansky E">EP Lansky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jeune, Mal" uniqKey="Jeune M">MAL Jeune</name></author><author><name sortKey="Kumi Diaka, J" uniqKey="Kumi Diaka J">J Kumi-Diaka</name></author><author><name sortKey="Brown, J" uniqKey="Brown J">J Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faria, A" uniqKey="Faria A">A Faria</name></author><author><name sortKey="Conceicao, C" uniqKey="Conceicao C">C Conceição</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Alcon, A" uniqKey="Alcon A">A Alcon</name></author><author><name sortKey="Yuan, H" uniqKey="Yuan H">H Yuan</name></author><author><name sortKey="Ho, J" uniqKey="Ho J">J Ho</name></author><author><name sortKey="Li, Q J" uniqKey="Li Q">Q-J Li</name></author><author><name sortKey="Martins Green, M" uniqKey="Martins Green M">M Martins-Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Burton, A" uniqKey="Burton A">A Burton</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adhami, Vm" uniqKey="Adhami V">VM Adhami</name></author><author><name sortKey="Siddiqui, Ia" uniqKey="Siddiqui I">IA Siddiqui</name></author><author><name sortKey="Syed, Dn" uniqKey="Syed D">DN Syed</name></author><author><name sortKey="Lall, Rk" uniqKey="Lall R">RK Lall</name></author><author><name sortKey="Mukhtar, H" uniqKey="Mukhtar H">H Mukhtar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Herszenyi, L" uniqKey="Herszenyi L">L Herszényi</name></author><author><name sortKey="Hritz, I" uniqKey="Hritz I">I Hritz</name></author><author><name sortKey="Lakatos, G" uniqKey="Lakatos G">G Lakatos</name></author><author><name sortKey="Varga, Mz" uniqKey="Varga M">MZ Varga</name></author><author><name sortKey="Tulassay, Z" uniqKey="Tulassay Z">Z Tulassay</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sarkar, Fh" uniqKey="Sarkar F">FH Sarkar</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Kong, D" uniqKey="Kong D">D Kong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sreeja, S" uniqKey="Sreeja S">S Sreeja</name></author><author><name sortKey="Santhosh Kumar, Tr" uniqKey="Santhosh Kumar T">TR Santhosh Kumar</name></author><author><name sortKey="Lakshmi, Bs" uniqKey="Lakshmi B">BS Lakshmi</name></author><author><name sortKey="Sreeja, S" uniqKey="Sreeja S">S Sreeja</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Etique, N" uniqKey="Etique N">N Etique</name></author><author><name sortKey="Grillier Vuissoz, I" uniqKey="Grillier Vuissoz I">I Grillier-Vuissoz</name></author><author><name sortKey="Flament, S" uniqKey="Flament S">S Flament</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Afaq, F" uniqKey="Afaq F">F Afaq</name></author><author><name sortKey="Malik, A" uniqKey="Malik A">A Malik</name></author><author><name sortKey="Syed, D" uniqKey="Syed D">D Syed</name></author><author><name sortKey="Maes, D" uniqKey="Maes D">D Maes</name></author><author><name sortKey="Matsui, Ms" uniqKey="Matsui M">MS Matsui</name></author><author><name sortKey="Mukhtar, H" uniqKey="Mukhtar H">H Mukhtar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, Ls" uniqKey="Adams L">LS Adams</name></author><author><name sortKey="Seeram, Np" uniqKey="Seeram N">NP Seeram</name></author><author><name sortKey="Aggarwal, Bb" uniqKey="Aggarwal B">BB Aggarwal</name></author><author><name sortKey="Takada, Y" uniqKey="Takada Y">Y Takada</name></author><author><name sortKey="Sand, D" uniqKey="Sand D">D Sand</name></author><author><name sortKey="Heber, D" uniqKey="Heber D">D Heber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Koyama, S" uniqKey="Koyama S">S Koyama</name></author><author><name sortKey="Cobb, Lj" uniqKey="Cobb L">LJ Cobb</name></author><author><name sortKey="Mehta, Hh" uniqKey="Mehta H">HH Mehta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fuhrman, B" uniqKey="Fuhrman B">B Fuhrman</name></author><author><name sortKey="Volkova, N" uniqKey="Volkova N">N Volkova</name></author><author><name sortKey="Aviram, M" uniqKey="Aviram M">M Aviram</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Nigris, F" uniqKey="De Nigris F">F de Nigris</name></author><author><name sortKey="Williams Ignarro, S" uniqKey="Williams Ignarro S">S Williams-Ignarro</name></author><author><name sortKey="Lerman, Lo" uniqKey="Lerman L">LO Lerman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aviram, M" uniqKey="Aviram M">M Aviram</name></author><author><name sortKey="Rosenblat, M" uniqKey="Rosenblat M">M Rosenblat</name></author><author><name sortKey="Gaitini, D" uniqKey="Gaitini D">D Gaitini</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azadzoi, Km" uniqKey="Azadzoi K">KM Azadzoi</name></author><author><name sortKey="Schulman, Rn" uniqKey="Schulman R">RN Schulman</name></author><author><name sortKey="Aviram, M" uniqKey="Aviram M">M Aviram</name></author><author><name sortKey="Siroky, Mb" uniqKey="Siroky M">MB Siroky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Esmaillzadeh, A" uniqKey="Esmaillzadeh A">A Esmaillzadeh</name></author><author><name sortKey="Tahbaz, F" uniqKey="Tahbaz F">F Tahbaz</name></author><author><name sortKey="Gaieni, I" uniqKey="Gaieni I">I Gaieni</name></author><author><name sortKey="Alavi Majd, H" uniqKey="Alavi Majd H">H Alavi-Majd</name></author><author><name sortKey="Azadbakht, L" uniqKey="Azadbakht L">L Azadbakht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aviram, M" uniqKey="Aviram M">M Aviram</name></author><author><name sortKey="Volkova, N" uniqKey="Volkova N">N Volkova</name></author><author><name sortKey="Coleman, R" uniqKey="Coleman R">R Coleman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jordan, Vc" uniqKey="Jordan V">VC Jordan</name></author><author><name sortKey="Phelps, E" uniqKey="Phelps E">E Phelps</name></author><author><name sortKey="Lindgren, Ju" uniqKey="Lindgren J">JU Lindgren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ke, Hz" uniqKey="Ke H">HZ Ke</name></author><author><name sortKey="Paralkak, Vm" uniqKey="Paralkak V">VM Paralkak</name></author><author><name sortKey="Grasser, Wa" uniqKey="Grasser W">WA Grasser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lerner, Lj" uniqKey="Lerner L">LJ Lerner</name></author><author><name sortKey="Jordan, Vc" uniqKey="Jordan V">VC Jordan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banu, J" uniqKey="Banu J">J Banu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sreekumar, S" uniqKey="Sreekumar S">S Sreekumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y Y" uniqKey="Kim Y">Y-Y Kim</name></author><author><name sortKey="Kim, S H" uniqKey="Kim S">S-H Kim</name></author><author><name sortKey="Oh, S" uniqKey="Oh S">S Oh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Neerup, Tsr" uniqKey="Neerup T">TSR Neerup</name></author><author><name sortKey="Stahlhut, M" uniqKey="Stahlhut M">M Stahlhut</name></author><author><name sortKey="Petersen, Js" uniqKey="Petersen J">JS Petersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Tranguch, S" uniqKey="Tranguch S">S Tranguch</name></author><author><name sortKey="Xie, H" uniqKey="Xie H">H Xie</name></author><author><name sortKey="Hanley, G" uniqKey="Hanley G">G Hanley</name></author><author><name sortKey="Das, Sk" uniqKey="Das S">SK Das</name></author><author><name sortKey="Dey, Sk" uniqKey="Dey S">SK Dey</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amini, Aa" uniqKey="Amini A">AA Amini</name></author><author><name sortKey="Nair, Ls" uniqKey="Nair L">LS Nair</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ignarro, Lj" uniqKey="Ignarro L">LJ Ignarro</name></author><author><name sortKey="Byrns, Re" uniqKey="Byrns R">RE Byrns</name></author><author><name sortKey="Sumi, D" uniqKey="Sumi D">D Sumi</name></author><author><name sortKey="De Nigris, F" uniqKey="De Nigris F">F de Nigris</name></author><author><name sortKey="Napoli, C" uniqKey="Napoli C">C Napoli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parmar, Hs" uniqKey="Parmar H">HS Parmar</name></author><author><name sortKey="Kar, A" uniqKey="Kar A">A Kar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Toklu, Hz" uniqKey="Toklu H">HZ Toklu</name></author><author><name sortKey="Dumlu, Mu" uniqKey="Dumlu M">MU Dumlu</name></author><author><name sortKey="Sehirli, O" uniqKey="Sehirli O">Ö Sehirli</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chidambara Murthy, Mkn" uniqKey="Chidambara Murthy M">MKN Chidambara Murthy</name></author><author><name sortKey="Jayaprakasha, Gk" uniqKey="Jayaprakasha G">GK Jayaprakasha</name></author><author><name sortKey="Singh, Rp" uniqKey="Singh R">RP Singh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shukla, M" uniqKey="Shukla M">M Shukla</name></author><author><name sortKey="Gupta, K" uniqKey="Gupta K">K Gupta</name></author><author><name sortKey="Rasheed, Z" uniqKey="Rasheed Z">Z Rasheed</name></author><author><name sortKey="Khan, Ka" uniqKey="Khan K">KA Khan</name></author><author><name sortKey="Haqqi, Tm" uniqKey="Haqqi T">TM Haqqi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Larrosa, M" uniqKey="Larrosa M">M Larrosa</name></author><author><name sortKey="Gonzalez Sarrias, A" uniqKey="Gonzalez Sarrias A">A González-Sarrías</name></author><author><name sortKey="Ya Ez Gasc N, Mj" uniqKey="Ya Ez Gasc N M">MJ Yáñez-Gascón</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, C J" uniqKey="Lee C">C-J Lee</name></author><author><name sortKey="Chen, L G" uniqKey="Chen L">L-G Chen</name></author><author><name sortKey="Liang, W L" uniqKey="Liang W">W-L Liang</name></author><author><name sortKey="Wang, C C" uniqKey="Wang C">C-C Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rasheed, Z" uniqKey="Rasheed Z">Z Rasheed</name></author><author><name sortKey="Akhtar, N" uniqKey="Akhtar N">N Akhtar</name></author><author><name sortKey="Anbazhagan, An" uniqKey="Anbazhagan A">AN Anbazhagan</name></author><author><name sortKey="Ramamurthy, S" uniqKey="Ramamurthy S">S Ramamurthy</name></author><author><name sortKey="Shukla, M" uniqKey="Shukla M">M Shukla</name></author><author><name sortKey="Haqqi, Tm" uniqKey="Haqqi T">TM Haqqi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Menezes, Sms" uniqKey="Menezes S">SMS Menezes</name></author><author><name sortKey="Cordeiro, Ln" uniqKey="Cordeiro L">LN Cordeiro</name></author><author><name sortKey="Viana, Gsb" uniqKey="Viana G">GSB Viana</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Souza Vasconcelos, Lc" uniqKey="De Souza Vasconcelos L">LC de Souza Vasconcelos</name></author><author><name sortKey="Correia Sampaio, Mc" uniqKey="Correia Sampaio M">MC Correia Sampaio</name></author><author><name sortKey="Correia Sampaio, F" uniqKey="Correia Sampaio F">F Correia Sampaio</name></author><author><name sortKey="Higino, Js" uniqKey="Higino J">JS Higino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ewies, Aaa" uniqKey="Ewies A">AAA Ewies</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, J Y" uniqKey="Hu J">J-Y Hu</name></author><author><name sortKey="Aizawa, T" uniqKey="Aizawa T">T Aizawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Setchell, Kdr" uniqKey="Setchell K">KDR Setchell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anderson, Jjb" uniqKey="Anderson J">JJB Anderson</name></author><author><name sortKey="Anthony, M" uniqKey="Anthony M">M Anthony</name></author><author><name sortKey="Messina, M" uniqKey="Messina M">M Messina</name></author><author><name sortKey="Garner, Sc" uniqKey="Garner S">SC Garner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shang, Y" uniqKey="Shang Y">Y Shang</name></author><author><name sortKey="Brown, M" uniqKey="Brown M">M Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yao, K" uniqKey="Yao K">K Yao</name></author><author><name sortKey="Jordan, Vc" uniqKey="Jordan V">VC Jordan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fisher, B" uniqKey="Fisher B">B Fisher</name></author><author><name sortKey="Dignam, J" uniqKey="Dignam J">J Dignam</name></author><author><name sortKey="Bryant, J" uniqKey="Bryant J">J Bryant</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cortesi, L" uniqKey="Cortesi L">L Cortesi</name></author><author><name sortKey="De Matteis, E" uniqKey="De Matteis E">E de Matteis</name></author><author><name sortKey="Rashid, I" uniqKey="Rashid I">I Rashid</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maru, I" uniqKey="Maru I">I Maru</name></author><author><name sortKey="Ohnishi, J" uniqKey="Ohnishi J">J Ohnishi</name></author><author><name sortKey="Yamaguchi, S" uniqKey="Yamaguchi S">S Yamaguchi</name></author><author><name sortKey="Oda, Y" uniqKey="Oda Y">Y Oda</name></author><author><name sortKey="Kakehi, K" uniqKey="Kakehi K">K Kakehi</name></author><author><name sortKey="Ohta, Y" uniqKey="Ohta Y">Y Ohta</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brower, V" uniqKey="Brower V">V Brower</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malik, A" uniqKey="Malik A">A Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dureja, H" uniqKey="Dureja H">H Dureja</name></author><author><name sortKey="Kaushik, D" uniqKey="Kaushik D">D Kaushik</name></author><author><name sortKey="Kumar, V" uniqKey="Kumar V">V Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tezcan, F" uniqKey="Tezcan F">F Tezcan</name></author><author><name sortKey="Gultekin Zguven, M" uniqKey="Gultekin Zguven M">M Gültekin-Özgüven</name></author><author><name sortKey="Diken, T" uniqKey="Diken T">T Diken</name></author><author><name sortKey="Ozcelik, B" uniqKey="Ozcelik B">B Özçelik</name></author><author><name sortKey="Erim, Fb" uniqKey="Erim F">FB Erim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Guo, C" uniqKey="Guo C">C Guo</name></author><author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name></author><author><name sortKey="Wei, J" uniqKey="Wei J">J Wei</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Cheng, S" uniqKey="Cheng S">S Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mirdehghan, Sh" uniqKey="Mirdehghan S">SH Mirdehghan</name></author><author><name sortKey="Rahemi, M" uniqKey="Rahemi M">M Rahemi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jahfar, M" uniqKey="Jahfar M">M Jahfar</name></author><author><name sortKey="Vijayan, Kk" uniqKey="Vijayan K">KK Vijayan</name></author><author><name sortKey="Azadi, P" uniqKey="Azadi P">P Azadi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, My" uniqKey="Hong M">MY Hong</name></author><author><name sortKey="Seeram, Np" uniqKey="Seeram N">NP Seeram</name></author><author><name sortKey="Heber, D" uniqKey="Heber D">D Heber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Disilvestro, Ra" uniqKey="Disilvestro R">RA DiSilvestro</name></author><author><name sortKey="Disilvestro, Dj" uniqKey="Disilvestro D">DJ DiSilvestro</name></author><author><name sortKey="Disilvestro, Dj" uniqKey="Disilvestro D">DJ DiSilvestro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seeram, Np" uniqKey="Seeram N">NP Seeram</name></author><author><name sortKey="Aviram, M" uniqKey="Aviram M">M Aviram</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelawala, Ns" uniqKey="Kelawala N">NS Kelawala</name></author><author><name sortKey="Ananthanarayan, L" uniqKey="Ananthanarayan L">L Ananthanarayan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sch Fer, A" uniqKey="Sch Fer A">A Schäfer</name></author><author><name sortKey="Chovanova, Z" uniqKey="Chovanova Z">Z Chovanová</name></author><author><name sortKey="Muchova, J" uniqKey="Muchova J">J Muchová</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seeram, Np" uniqKey="Seeram N">NP Seeram</name></author><author><name sortKey="Adams, Ls" uniqKey="Adams L">LS Adams</name></author><author><name sortKey="Henning, Sm" uniqKey="Henning S">SM Henning</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Meenakshi, S" uniqKey="Meenakshi S">S Meenakshi</name></author><author><name sortKey="Kalpana, G" uniqKey="Kalpana G">G Kalpana</name></author><author><name sortKey="Khursheed, Ak" uniqKey="Khursheed A">AK Khursheed</name></author><author><name sortKey="Tariq, Mh" uniqKey="Tariq M">MH Tariq</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">Biomed Res Int</journal-id><journal-id journal-id-type="iso-abbrev">Biomed Res Int</journal-id><journal-id journal-id-type="publisher-id">BMRI</journal-id><journal-title-group><journal-title>BioMed Research International</journal-title></journal-title-group><issn pub-type="ppub">2314-6133</issn><issn pub-type="epub">2314-6141</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24818149</article-id><article-id pub-id-type="pmc">4000966</article-id><article-id pub-id-type="doi">10.1155/2014/686921</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title>Pomegranate Fruit as a Rich Source of Biologically Active Compounds</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Sreekumar</surname><given-names>Sreeja</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Sithul</surname><given-names>Hima</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Muraleedharan</surname><given-names>Parvathy</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Azeez</surname><given-names>Juberiya Mohammed</given-names></name><xref ref-type="aff" rid="I1"></xref></contrib><contrib contrib-type="author"><name><surname>Sreeharshan</surname><given-names>Sreeja</given-names></name><xref ref-type="aff" rid="I1"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="I1">Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thycaud P.O, Thiruvananthapuram, Kerala 695 014, India</aff><author-notes><corresp id="cor1">*Sreeja Sreeharshan: <email>sreejasreeharshan@yahoo.com</email></corresp><fn fn-type="other"><p>Academic Editor: Kota V. Ramana</p></fn></author-notes><pub-date pub-type="ppub"><year>2014</year></pub-date><pub-date pub-type="epub"><day>10</day><month>4</month><year>2014</year></pub-date><volume>2014</volume><elocation-id>686921</elocation-id><history><date date-type="received"><day>21</day><month>11</month><year>2013</year></date><date date-type="rev-recd"><day>25</day><month>2</month><year>2014</year></date><date date-type="accepted"><day>25</day><month>2</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 Sreeja Sreekumar et al.</copyright-statement><copyright-year>2014</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on <italic>Punica</italic>. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20–320 <italic><italic>μ</italic></italic>g/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17<italic><italic>β</italic></italic>-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells.
The results indicated that PME (80 <italic><italic>μ</italic></italic>g/mL) significantly increased ALP
(Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation.
The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model.
The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds. </p></abstract></article-meta></front><body><sec id="sec1"><title>1. Introduction</title><p><italic>Punica granatum </italic>L. (Punicaceae) is a nutrient dense fruit rich in phytochemical compounds [<xref rid="B1" ref-type="bibr">1</xref>]. Plants produce low molecular weight compounds which are broadly called phytochemicals, usually as a mechanism of defence. Some plants contain distinct families of phytocompounds, which are structurally similar to steroid hormone, 17<italic>β</italic>-estradiol (E2) and compete with the endogenous hormone for binding to estrogen receptor (ER), thus reducing the hormonal effect of endogenous estrogens [<xref rid="B2" ref-type="bibr">2</xref>–<xref rid="B4" ref-type="bibr">4</xref>]. These compounds are termed as phytoestrogens. Most of these phytoestrogens present in the diet are inactive compounds, which, on consumption, go through series of enzymatic changes in the gastrointestinal tract, resulting in the formation of compounds having structure similar to that of estrogens [<xref rid="B5" ref-type="bibr">5</xref>]. Phytoestrogens have captured major research and clinical attention due to its effectiveness in the prevention and treatment of perimenopausal and menopausal symptoms, over hormone replacement therapy (HRT) [<xref rid="B6" ref-type="bibr">6</xref>]. They may act both as agonists and/or antagonists in a site-specific manner, similar to the hormonal action of selective estrogen receptor modulators (SERMs) [<xref rid="B7" ref-type="bibr">7</xref>–<xref rid="B9" ref-type="bibr">9</xref>]. It can also function as antioxidants and protect DNA from oxidant-induced damage [<xref rid="B10" ref-type="bibr">10</xref>]. Research on pomegranate is gaining momentum due to its tremendous nutritional values and medicinal uses. The current review focuses on the use of pomegranate as a phytoestrogen rich and nutraceutical fruit with emphasis to the work done in our laboratory using methanolic extract of pericarp of pomegranate (PME).</p></sec><sec id="sec2"><title>2. Chemical Constituents of Pomegranate Fruit and Tree</title><p>The chemical composition of the fruits differs depending on the cultivar, growing region, maturity, cultivation practice, climate, and storage circumstances [<xref rid="B11" ref-type="bibr">11</xref>]. About 50% of the total fruit weight corresponds to the peel, which is an important source of bioactive compounds such as phenolics, flavonoids, ellagitannins, and proanthocyanidin compounds, minerals, mainly potassium, nitrogen, calcium, phosphorus, magnesium, and sodium, and complex polysaccharides. The edible part of the pomegranate fruit (50%) consists of 40% arils and 10% seeds. Arils contain 85% water, 10% total sugars, mainly fructose and glucose, and 1.5% pectin, organic acid, such as ascorbic acid, citric acid, and malic acid, and bioactive compounds such as phenolics and flavonoids, principally anthocyanins [<xref rid="B12" ref-type="bibr">12</xref>]. The seed cover of the fruit contains delphinidin-3-glucoside, cyanidin-3-glucoside, delphinidin-3,5-diglucoside, cyanidin-3,5-diglucoside, pelargonidin-3,5-diglucoside, and pelargonidin-3-glucoside with delphinidin-3,5-diglucoside being the main anthocyanin in pomegranate juice [<xref rid="B13" ref-type="bibr">13</xref>]. 12–20% of total seed weight of pomegranate comprises seed oil and is self-possessed with more than 70% of the conjugated linolenic acids. The fatty acid component of pomegranate seed oil comprises over 95% of the oil, of which 99% is triacylglycerols. Minor components of the oil include sterols, steroids, and a key component of mammalian myelin sheaths, cerebroside [<xref rid="B14" ref-type="bibr">14</xref>, <xref rid="B15" ref-type="bibr">15</xref>]. Interestingly, punicic acid, which is a conjugated isomer unique to pomegranate oil, constitutes 70–76% of the seed oil [<xref rid="B16" ref-type="bibr">16</xref>]. Phenolic compounds, together with flavonoids, anthocyanins, and tannins, are the main group of antioxidant phytochemicals that are important due to their biological and free radical scavenging activities [<xref rid="B17" ref-type="bibr">17</xref>]. Phenolic acids, flavonoids, and tannins are present in different parts of pomegranate fruit and this may be one of the reasons why many of the studies demonstrated that combinations of pomegranate extracts from different parts of the fruit were more effective than a single extract [<xref rid="B18" ref-type="bibr">18</xref>]. In a comparative analysis, anthocyanins from pomegranate fruit were found to possess higher antioxidant activity than vitamin-E (<italic>α</italic>-tocopherol), <italic>β</italic>-carotene, and ascorbic acid [<xref rid="B19" ref-type="bibr">19</xref>]. <xref ref-type="table" rid="tab1"> Table 1</xref> represents the key constituents of pomegranate fruit and tree [<xref rid="B20" ref-type="bibr">20</xref>–<xref rid="B41" ref-type="bibr">41</xref>].</p></sec><sec id="sec3"><title>3. Therapeutic Functions of Pomegranate</title><p>Extracts of all parts of the pomegranate fruit exhibit therapeutic properties [<xref rid="B15" ref-type="bibr">15</xref>] and target a range of diseases including cancer, cardiovascular disorders, diabetes, male infertility, Alzheimer's disease [<xref rid="B42" ref-type="bibr">42</xref>], aging, and AIDS [<xref rid="B43" ref-type="bibr">43</xref>] (<xref ref-type="fig" rid="fig1">Figure 1</xref>). Although pomegranate's extensive therapeutic benefits may be attributed to a number of mechanisms, most researchers have determined its antioxidant, anticarcinogenic, and anti-inflammatory properties. Various therapeutic applications of<italic> Punica granatum</italic> are discussed here.</p><sec id="sec3.1"><title>3.1. Cancer</title><p>Research on breast cancer cell lines demonstrated that pomegranate constituents efficiently inhibited angiogenesis [<xref rid="B44" ref-type="bibr">44</xref>], invasiveness [<xref rid="B40" ref-type="bibr">40</xref>], growth [<xref rid="B45" ref-type="bibr">45</xref>], and induced apoptosis [<xref rid="B46" ref-type="bibr">46</xref>]. Its anti-invasive, antiproliferative, and antimetastatic effects were attributed to the modulation of Bcl-2 proteins, upregulation of p27 and p21, and downregulation of cyclin-cdk network [<xref rid="B47" ref-type="bibr">47</xref>]. Pomegranate constituents inhibit angiogenesis via downregulation of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial and MCF-7 breast cancer cell lines [<xref rid="B44" ref-type="bibr">44</xref>], thereby hampering the tumor growth. Prostate cancer cells, when treated with pomegranate juice, increased adhesion and decreased the migration. Molecular analyses revealed that pomegranate juice increased the expression of cell-adhesion related genes and inhibited the expression of genes involved in cytoskeletal function and cellular migration. It would possibly affect prostate cancer because of its apoptotic, antioxidant, antiproliferative, and anti-inflammatory properties, suggesting that it may be beneficial in slowing down or preventing cancer cell metastasis [<xref rid="B48" ref-type="bibr">48</xref>]. The application of pomegranate extract to the skin of mice before they were exposed to a carcinogenic agent was shown to inhibit the appearance of erythemas and hyperplasia and the activity of epithelial ornithine decarboxylase [<xref rid="B49" ref-type="bibr">49</xref>]. An<italic> in vivo</italic> study in TRAMP mice model suggested that oral supplementation of pomegranate fruit extract inhibited metastasis and increased overall survival [<xref rid="B50" ref-type="bibr">50</xref>].</p><p>Matrix metalloproteinases (MMPs) are good markers of tumor cell invasion and migration [<xref rid="B51" ref-type="bibr">51</xref>]. Phytochemicals have been shown to target the activity and secretion of MMPs in estrogen responsive cancers [<xref rid="B52" ref-type="bibr">52</xref>]. Constituents of pomegranate minimize tumor cell invasion into normal tissue and metastasis to distant sites and these actions develop due to the inhibition of selected metalloproteinase activity, decreased focal adhesion kinase activity, and reduced VEGF expression [<xref rid="B15" ref-type="bibr">15</xref>]. With semiquantitative RT-PCR, we had found out that PME downregulated the transcription of MMP-9 suggesting its possible role in the inhibition of tumor invasion (<xref ref-type="fig" rid="fig2">Figure 2</xref>) whereas E2 (10 nM) did not significantly affect the transcription of MMP-9 [<xref rid="B53" ref-type="bibr">53</xref>] which correlated with earlier studies suggesting that estrogen stimulated MMP-9 secretion without increasing its gene transcription [<xref rid="B54" ref-type="bibr">54</xref>].</p><p>We had assessed the estrogenicity/antiestrogenicity of PME in a panel of<italic> in vitro</italic> biological assays and the expression of endogenous estrogen sensitive markers (pS2 and PR) in breast carcinoma cell lines were analyzed [<xref rid="B53" ref-type="bibr">53</xref>]. When MCF-7 cells pretreated with PME were treated with estrogen, the c-Myc expression was not induced as much as when treated with estrogen alone, demonstrating the effect of PME in estrogen regulated mechanism (<xref ref-type="fig" rid="fig3">Figure 3</xref>). ER positive cells treated with PPT (4,4′,4′′-(4-Propyl-(1<italic>H</italic>)-pyrazole-1,3,5-triyl)<italic>tris</italic>phenol) (ER<italic>α</italic> selective agonist) and DPN (Diarylpropionitrile) (ER<italic>β</italic> selective agonist) clearly showed that PPT increased the pS2 protein levels, whereas DPN did not produce any significant effect. When given in combination with PPT, PME reduced the pS2 protein levels indicating the role of ER<italic>α</italic> in mediating the effects of PME on pS2 expression (<xref ref-type="fig" rid="fig4">Figure 4</xref>). Thus the effect of PME on expression of pS2 was mediated by ER<italic>α</italic> and not by ER<italic>β</italic> [<xref rid="B53" ref-type="bibr">53</xref>].</p><p>Pomegranate fruit extract was revealed to inhibit UV-B-mediated phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor NF-<italic>κ</italic>B activation [<xref rid="B55" ref-type="bibr">55</xref>]. Pomegranate juice almost downregulated the TNF<italic>α</italic> induced Akt (protein kinase B) activation required for NF-<italic>κ</italic>B activity [<xref rid="B56" ref-type="bibr">56</xref>]. Koyama et al. [<xref rid="B57" ref-type="bibr">57</xref>] examined the effects of pomegranate extract (POMx) on the IGF system and found out cell growth inhibition and apoptosis. Their findings suggested that POMx treatment reduced mTOR phosphorylation at Ser2448 and Ser2481, whereas IGFBP-3 increased phosphorylation at those sites. These results suggested that POMx decreased prostate cancer cell survival by inhibiting IGF1 expression. To conclude, pomegranate fruit has anticancer properties that can be attributed to different mechanisms.</p></sec><sec id="sec3.2"><title>3.2. Cardiovascular Disorders</title><p><italic>In vitro</italic>,<italic> in vivo</italic> and human trials had examined the effects of a range of pomegranate constituents on the prevention and reduction of atherosclerosis and LDL oxidation [<xref rid="B58" ref-type="bibr">58</xref>]. Evidence suggested that polyphenolic antioxidants contained in pomegranate juice can cause reduction of oxidative stress and atherogenesis through the activation of redox-sensitive genes ELK-1 and p-JUN and increased eNOS expression. Their results indicated that proatherogenic effects induced by disturbed shear stress can be reversed by constant administration of pomegranate juice [<xref rid="B59" ref-type="bibr">59</xref>]. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduced common blood pressure, LDL oxidation, and carotid intima-media thickness [<xref rid="B60" ref-type="bibr">60</xref>]. Azadzoi et al. demonstrated that 8-week administration of pomegranate juice concentrate daily in a rabbit model of arteriogenic erectile dysfunction significantly increased intracavernous blood flow and smooth muscle relaxation, probably via its antioxidant effect on enhanced nitric oxide preservation and bioavailability [<xref rid="B61" ref-type="bibr">61</xref>]. A pilot study in type 2 diabetic patients with hyperlipidemia found that concentrated pomegranate juice decreased cholesterol absorption, increased faecal excretion of cholesterol, had a favourable effect on enzymes concerned in cholesterol metabolism, drastically reduced LDL cholesterol, and improved LDL/HDL cholesterol and total/HDL ratios [<xref rid="B62" ref-type="bibr">62</xref>]. Aviram et al. analyzed atherosclerotic lesion size, antioxidant activity, blood sugar, peritoneal macrophages, oxidative status, and lipid profiles for 3 months after giving 6 different pomegranate preparations with varying amounts of total polyphenols and gallic acid content in atherosclerotic apolipoprotein-E deficient mice and found that pomegranate phenolics and pomegranate unique complexed sugars could mimic the antiatherogenic effects of pomegranate extracts [<xref rid="B63" ref-type="bibr">63</xref>]. All these evidences suggest the potential cardioprotective effect of pomegranate fruit.</p></sec><sec id="sec3.3"><title>3.3. Antiosteoporotic Potential</title><p>Tissue selective estrogen agonist/antagonists are currently being investigated as alternatives to estrogen in the prevention and treatment of postmenopausal osteoporosis [<xref rid="B64" ref-type="bibr">64</xref>–<xref rid="B66" ref-type="bibr">66</xref>]. Bone loss after ovariectomy is associated with high bone turnover where bone resorption rate exceeds the bone formation rate [<xref rid="B67" ref-type="bibr">67</xref>]. To assess the protective role of<italic> Punica</italic> on skeletal system, we had examined the effect of PME on a well-characterized osteoblastic cell population (osteoblastic MC3T3-E1 cells) and examined its effect on Alkaline Phosphatase (ALP), which is a commonly used bone remodelling marker. The results (<xref ref-type="fig" rid="fig5">Figure 5</xref>) indicated that PME significantly increased ALP activity, supporting its suggested role in modulating osteoblastic cell differentiation [<xref rid="B68" ref-type="bibr">68</xref>].</p><p>Ovariectomized rodent model is a well-established system for estrogen deficiency induced bone loss and used by researchers previously [<xref rid="B69" ref-type="bibr">69</xref>, <xref rid="B70" ref-type="bibr">70</xref>]. We had evaluated the antiosteoporotic potential of the extract in estrogen deficiency induced osteoporosis in young adult mice of 6–8 weeks of age by assessing the bone turnover by serum ALP. In comparison to the sham surgery (SS) control, ovariectomized (Ovx) control animals showed an increase in ALP activity indicating an increase in bone turn-over rate in these animals. PME in higher concentration was found to be effective in decreasing this bone turnover, though E2 was better in controlling the accelerated bone turnover (<xref ref-type="table" rid="tab2">Table 2</xref>). The experimental model differed from aged Ovx mice wherein the osteoporosis is induced only by estrogen deficiency and not by a combination of natural bone loss due to age and ovarian hormone deficiency. An increase in bone turn-over rate was indicated by higher serum ALP level in the Ovx group compared to the SS control group. Therefore, high rate of bone turnover was well corrected by PME suggesting that it might play a protective role against ovarian hormone insufficiency related bone resorption. But E2 as well as PME was able to significantly decrease ALP levels in Ovx mice (<xref ref-type="table" rid="tab2">Table 2</xref>). Serum calcium and phosphorous levels in Ovx control, PME treated, and tamoxifen treated animals were similar to that of SS control animals. Significant decrease in calcium levels was observed in E2 treated animals in comparison to SS control (<xref ref-type="table" rid="tab2">Table 2</xref>). Our findings clearly indicated that the possible bone preserving effect of PME is almost comparable with E2 [<xref rid="B53" ref-type="bibr">53</xref>]. Earlier studies had shown that an acute or chronic exposure to xenoestrogens or dietary phytoestrogens alters uterine expression of estrogen sensitive genes in mice [<xref rid="B71" ref-type="bibr">71</xref>]. So in order to check whether PME has any effect, a semiquantitative RT-PCR was done to analyze uterine mRNA levels of lactoferrin in ovariectomized mice fed with PME for 7 days. Lactoferrin is a well-known estrogen target gene and a biologically active molecule for bone regeneration [<xref rid="B72" ref-type="bibr">72</xref>]. The positive control E2 increased the uterine accumulation of lactoferrin mRNA in Ovx animals compared to the vehicle treated Ovx control (<xref ref-type="fig" rid="fig6">Figure 6</xref>). Lactoferrin expression did not differ significantly between the groups that received PME (50, 100 mg/kg bwt) and the vehicle (0.1% ethanol) treated Ovx control group, indicating the lack of estrogenicity of PME on uterine endometrium in the doses tested in our study. Tamoxifen (10 mg/kg bwt) was found to increase the expression of lactoferrin, though not significantly [<xref rid="B68" ref-type="bibr">68</xref>]. As there are promising results from both<italic> in vitro</italic> and<italic> in vivo</italic> studies, we suggest evaluating the antiosteoporotic potential by clinical trials with pomegranate fruit extract that has no side effects on uterine endometrium alongside a significant decrease in bone turn-over rate.</p></sec><sec id="sec3.4"><title>3.4. Other Clinical Applications</title><p><italic>In vitro </italic>assay showed that fermented pomegranate juice extract is better than red wine and comparable to green tea [<xref rid="B37" ref-type="bibr">37</xref>]. There were also reports that pomegranate juice possessed considerably greater antioxidant capacity at much lower concentrations (>1000-fold dilutions) than either grape or blueberry juice [<xref rid="B73" ref-type="bibr">73</xref>].<italic> Punica granatum </italic>peel extract decreased lipid peroxidation in hepatic, cardiac, and renal tissues and at the same time it had a facilitatory effect on the scavenging capability of superoxide anion and hydrogen peroxide [<xref rid="B74" ref-type="bibr">74</xref>]. Formerly, it was shown that pomegranate peel extract supplementation alleviated oxidative damage of the liver and enhanced the hepatic structure and function in rats exposed to bile duct ligation [<xref rid="B75" ref-type="bibr">75</xref>]. Pretreatment of carbon tetrachloride-induced liver damage in rats with pomegranate peel extract resulted in the reduction of lipid peroxidation and at the same time, the free-radical scavenging activity of catalase, superoxide dismutase, and peroxidase were considerably enhanced [<xref rid="B76" ref-type="bibr">76</xref>]. Many studies had keenly explored the anti-inflammatory properties of pomegranate fruit [<xref rid="B15" ref-type="bibr">15</xref>, <xref rid="B77" ref-type="bibr">77</xref>–<xref rid="B79" ref-type="bibr">79</xref>]. Studies indicated that pomegranate extract inhibited PMACI-induced proinflammatory cytokines assembly by inhibiting the gene expression. This is achieved by blocking JNK and ERK-MAPK activation and NF-<italic>κ</italic>B activation in human KU812 cells [<xref rid="B80" ref-type="bibr">80</xref>]. Larrosa et al. showed that pomegranate extract supplementations led to reduced prostaglandin E2 (PGE2) levels in the colon mucosa by downregulating the overexpressed COX-2 and prostaglandin E synthase (PTGES) levels owing to the action of ellagic acid [<xref rid="B78" ref-type="bibr">78</xref>].<italic> Punica granatum </italic>extract had been found to be particularly effective for controlling oral inflammation, dental plaque, and bacterial and fungal counts in periodontal disease and Candida-associated denture stomatitis [<xref rid="B81" ref-type="bibr">81</xref>, <xref rid="B82" ref-type="bibr">82</xref>]. Another study proposed that inhibition of number of signal transduction pathways and the downstream pathogenic cellular response by pomegranate extract or compounds may be a useful approach for the prevention of the onset and severity of inflammatory arthritis [<xref rid="B77" ref-type="bibr">77</xref>]. The dynamism of pomegranate fruit in newer areas of pharmacological effects might be delivered in the future.</p></sec></sec><sec id="sec4"><title>4. Pomegranate Extract as a Phytoestrogen</title><p>Due to the possible adverse side effects of estrogenic stimulation (such as increase in tumor risk), many women have turned to phytoestrogens as an alternative for HRT [<xref rid="B83" ref-type="bibr">83</xref>]. The features that facilitate the chemicals to bind with ER are the steric and hydrophobic properties of a compound, as well as the hydrogen bonding between the phenolic hydroxyl group and the ER binding site [<xref rid="B84" ref-type="bibr">84</xref>]. Phytoestrogens bind to both forms of ER and showed a lower binding affinity than E2. Some of them exhibit a higher binding affinity to ER<italic>β</italic> than to ER<italic>α</italic> which may indicate that they have different pathways for their actions and explains tissue specific changeability in phytoestrogenic action [<xref rid="B85" ref-type="bibr">85</xref>]. Both genomic and nongenomic mechanisms have been projected to explain phytoestrogenic effects on human health [<xref rid="B86" ref-type="bibr">86</xref>]. The best move towards the avoidance and handling of estrogen-dependent breast cancer is to selectively hold estrogen activity in the affected tissues without compromising its beneficial effects [<xref rid="B87" ref-type="bibr">87</xref>]. Regrettably, at this time, available antiestrogen such as tamoxifen used in the treatment of ER-positive breast cancer has side effects and agonism in the uterine endometrium, leading to an uncertain connection to endometrial carcinoma [<xref rid="B88" ref-type="bibr">88</xref>–<xref rid="B90" ref-type="bibr">90</xref>]. A competitive radioactive binding study was done to ascertain whether PME interacts with ER and had shown that PME binds to ER and inhibited the binding of labelled estrogen to ER in a dose-dependent manner [<xref rid="B53" ref-type="bibr">53</xref>, <xref rid="B91" ref-type="bibr">91</xref>].</p></sec><sec id="sec5"><title>5. Pomegranate as a Potential Nutraceutical</title><p>According to De Felice, who coined the term nutraceutical, it can be defined as, “a food (or part of a food) that provides medical or health benefits, including the prevention and/or treatment of a disease” [<xref rid="B92" ref-type="bibr">92</xref>]. It may range from isolated nutrients, herbal products, dietary supplements, and diets to genetically engineered “designer” foods and processed products such as cereals, soups, and beverages [<xref rid="B93" ref-type="bibr">93</xref>, <xref rid="B94" ref-type="bibr">94</xref>]. Anthocyanidins (delphinidin, cyanidin, and pelargonidin) and hydrolysable tannins (such as punicalagin, pedunculagin, punicalin, gallagic, and ellagic acid esters of glucose), account for the major antioxidant activity of whole fruit [<xref rid="B22" ref-type="bibr">22</xref>, <xref rid="B95" ref-type="bibr">95</xref>]. The peel, which is also a major part of the fruit, is an imperative source of bioactive compounds such as phenolics, flavonoids, ellagitannins, proanthocyanidin compounds [<xref rid="B96" ref-type="bibr">96</xref>], minerals, [<xref rid="B97" ref-type="bibr">97</xref>], and complex polysaccharides [<xref rid="B98" ref-type="bibr">98</xref>]. Aviram and others reported that systolic blood pressure was reduced, after 1 year of pomegranate juice consumption. This was believed to be related to the potent antioxidant properties of pomegranate polyphenols [<xref rid="B60" ref-type="bibr">60</xref>]. Hong et al. confirmed that pomegranate juice and pomegranate extracts were more potent inhibitors of cell growth than isolated individual polyphenols in cell lines, influential synergistic and/or additive effects of several phytochemicals including proanthocyanidins, anthocyanins, and flavonoid glycosides [<xref rid="B99" ref-type="bibr">99</xref>]. Pomegranate contains agents, particularly polyphenolic flavonoids, which exert actions that could be well conducive to good oral health, particularly in relation to gingivitis development [<xref rid="B100" ref-type="bibr">100</xref>]. Pomegranate juice had the greatest antioxidant potency composite index among beverages like black cherry juice, cranberry juice, grape juice, apple juice, orange juice, red wines, blueberry juice, and iced tea; and the antioxidant activity was at least 20% superior to any of the other beverages tested [<xref rid="B101" ref-type="bibr">101</xref>–<xref rid="B103" ref-type="bibr">103</xref>]. Each and every part of pomegranate provides health benefits, that is, a nutraceutical food.</p></sec><sec id="sec6"><title>6. Summary and Conclusions</title><p>The discovery that plants generate hormonally active phytochemicals has altered our understanding of the connection between diet and human health. It is well established that fruit or plant extracts are a complex mixture of various constituents and, in most of the instances, it is not clear whether a single compound or a mixture of compounds is responsible for the reported effects [<xref rid="B104" ref-type="bibr">104</xref>]. The thought of the whole herb or multiherb preparation not only addresses multiple targets, but possibly will alleviate the toxicity and side effects of a single, isolated compound from the plant. Many<italic> in vitro</italic> and<italic> in vivo</italic> studies pointed out high nutritional and potential tissue specific action of extract of<italic> Punica granatum</italic>. Proofs are accumulating that compounds present in a fruit or herb extract augment each other's biological effect. For example, it has been reported that quercetin and ellagic acid (both are also present in pomegranate) together make use of a more prominent inhibitory effect against cancer cell growth than either compound alone [<xref rid="B105" ref-type="bibr">105</xref>]. We had found that PME has antiestrogenic effect in the mammary gland, without compromising the beneficial effects of estrogen in the cardiovascular and skeletal system and had no estrogenicity in the uterus [<xref rid="B53" ref-type="bibr">53</xref>]. PME could possibly be considered as an ideal SERM and further studies might demonstrate its suitability and possible application in estrogen dependent breast cancers with beneficial effects in other hormone dependent tissues. <xref ref-type="fig" rid="fig7"> Figure 7</xref> describes the biological effects of PME, as observed in our studies. Furthermore, it would be valuable to investigate the long-term effects of PME in the<italic> in vivo</italic> models of estrogen deprivation to demonstrate its suitability in HRT. To achieve this goal, a better understanding is needed regarding the orchestrated action of SERM, receptor and coregulators that contribute to distinct patterns of gene expression. Although scientific research is being carried out to study the biological activity of a lot of food phytochemicals, the health claims attributed to the final marketed nutraceutical products have normally little or doubtful scientific foundation. This is owing to the fact that a great deal of scientific conclusion is derived from animal testing and<italic> in vitro</italic> assays, while human clinical trials are limited. Some key issues such as metabolism, bioavailability, toxicity, and dose/response of these food bioactive compounds or nutraceuticals themselves have not been well recognized yet. Currently, numerous clinical trials are in progress exploring the therapeutic potential of pomegranate extracts. Its potential use as a nutraceutical needs to be investigated. We may thus anticipate that many of the open issues about the biological effect of extract of<italic> Punica granatum</italic> will be answered in the near future.</p></sec></body><back><ack><title>Acknowledgments</title><p>The authors gratefully appreciate the support by grants from Kerala State Planning Board, Government of Kerala, India. Mrs. Sreeja Sreekumar was supported by Indian Council of Medical Research (ICMR), Government of India (Senior Research Fellowship), and Mrs. Parvathy Muraleedharan by Senior Research Fellowship from the Council of Scientific and Industrial Research, Government of India (CSIR award no. 09/716(0125)/2009-EMR-I). The views and opinions expressed in this paper are those of the authors.</p></ack><sec><title>Authors' Contribution</title><p>Sreeja Sreekumar, Hima Sithul, Parvathy Muraleedharan, and Juberiya Mohammed Azeez have equal authorship.</p></sec><sec sec-type="conflict"><title>Conflict of Interests</title><p>The authors declare that there is no conflict of interests regarding the publication of this paper.</p></sec><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miguel</surname><given-names>MG</given-names></name><name><surname>Neves</surname><given-names>MA</given-names></name><name><surname>Antunes</surname><given-names>MD</given-names></name></person-group><article-title>Pomegranate (<italic>Punica granatum</italic> L.): a medicinal plant with myriad biological properties—a short review</article-title><source><italic>Journal of Medicinal Plant Research</italic></source><year>2010</year><volume>4</volume><issue>25</issue><fpage>2836</fpage><lpage>2847</lpage><pub-id pub-id-type="other">2-s2.0-79251590557</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elghamry</surname><given-names>MI</given-names></name><name><surname>Shihata</surname><given-names>IM</given-names></name></person-group><article-title>Biological activity of phytoestrogens. 3. Experimental studies on some biological properties of beta-sitosterol</article-title><source><italic>Planta Medica</italic></source><year>1966</year><volume>14</volume><issue>3</issue><fpage>352</fpage><lpage>357</lpage><pub-id pub-id-type="other">2-s2.0-0013937359</pub-id><pub-id pub-id-type="pmid">6008897</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Magee</surname><given-names>PJ</given-names></name><name><surname>Rowland</surname><given-names>IR</given-names></name></person-group><article-title>Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer</article-title><source><italic>The British Journal of Nutrition</italic></source><year>2004</year><volume>91</volume><issue>4</issue><fpage>513</fpage><lpage>531</lpage><pub-id pub-id-type="other">2-s2.0-2342649469</pub-id><pub-id pub-id-type="pmid">15035679</pub-id></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barnes</surname><given-names>S</given-names></name></person-group><article-title>Phytoestrogens and breast cancer</article-title><source><italic>Bailliere’s Clinical Endocrinology and Metabolism</italic></source><year>1998</year><volume>12</volume><issue>4</issue><fpage>559</fpage><lpage>579</lpage><pub-id pub-id-type="other">2-s2.0-0032450923</pub-id></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adlercreutz</surname><given-names>H</given-names></name></person-group><article-title>Phyto-oestrogens and cancer</article-title><source><italic>The Lancet Oncology</italic></source><year>2002</year><volume>3</volume><issue>6</issue><fpage>364</fpage><lpage>373</lpage><pub-id pub-id-type="other">2-s2.0-0036072803</pub-id><pub-id pub-id-type="pmid">12107024</pub-id></element-citation></ref><ref id="B6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Glazier</surname><given-names>MG</given-names></name><name><surname>Bowman</surname><given-names>MA</given-names></name></person-group><article-title>A review of the evidence for the use of phytoestrogens as a replacement for traditional estrogen replacement therapy</article-title><source><italic>Archives of Internal Medicine</italic></source><year>2001</year><volume>161</volume><issue>9</issue><fpage>1161</fpage><lpage>1172</lpage><pub-id pub-id-type="other">2-s2.0-0034923423</pub-id><pub-id pub-id-type="pmid">11343439</pub-id></element-citation></ref><ref id="B7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brzezinski</surname><given-names>A</given-names></name><name><surname>Debi</surname><given-names>A</given-names></name></person-group><article-title>Phytoestrogens: the “natural” selective estrogen receptor modulators?</article-title><source><italic>European Journal of Obstetrics Gynecology and Reproductive Biology</italic></source><year>1999</year><volume>85</volume><issue>1</issue><fpage>47</fpage><lpage>51</lpage><pub-id pub-id-type="other">2-s2.0-0032994684</pub-id></element-citation></ref><ref id="B8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Halbreich</surname><given-names>U</given-names></name><name><surname>Kahn</surname><given-names>LS</given-names></name></person-group><article-title>Selective oestrogen receptor modulators current and future brain and behaviour applications</article-title><source><italic>Expert Opinion on Pharmacotherapy</italic></source><year>2000</year><volume>1</volume><issue>7</issue><fpage>1385</fpage><lpage>1398</lpage><pub-id pub-id-type="other">2-s2.0-0034568956</pub-id><pub-id pub-id-type="pmid">11249472</pub-id></element-citation></ref><ref id="B9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hol</surname><given-names>T</given-names></name><name><surname>Cox</surname><given-names>MB</given-names></name><name><surname>Bryant</surname><given-names>HU</given-names></name><name><surname>Draper</surname><given-names>MW</given-names></name></person-group><article-title>Selective estrogen receptor modulators and postmenopausal women’s health</article-title><source><italic>Journal of Women’s Health</italic></source><year>1997</year><volume>6</volume><issue>5</issue><fpage>523</fpage><lpage>531</lpage><pub-id pub-id-type="other">2-s2.0-37849189323</pub-id></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sierens</surname><given-names>J</given-names></name><name><surname>Hartley</surname><given-names>JA</given-names></name><name><surname>Campbell</surname><given-names>MJ</given-names></name><name><surname>Leathem</surname><given-names>AJC</given-names></name><name><surname>Woodside</surname><given-names>JV</given-names></name></person-group><article-title>Effect of phytoestrogen and antioxidant supplementation on oxidative DNA damage assessed using the comet assay</article-title><source><italic>Mutation Research: DNA Repair</italic></source><year>2001</year><volume>485</volume><issue>2</issue><fpage>169</fpage><lpage>176</lpage><pub-id pub-id-type="other">2-s2.0-0035820073</pub-id><pub-id pub-id-type="pmid">11182547</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fadavi</surname><given-names>A</given-names></name><name><surname>Barzegar</surname><given-names>M</given-names></name><name><surname>Azizi</surname><given-names>MH</given-names></name><name><surname>Bayat</surname><given-names>M</given-names></name></person-group><article-title>Physicochemical composition of ten pomegranate cultivars (<italic>Punica granatum</italic> L.) grown in Iran</article-title><source><italic>Food Science and Technology International</italic></source><year>2005</year><volume>11</volume><issue>2</issue><fpage>113</fpage><lpage>119</lpage><pub-id pub-id-type="other">2-s2.0-20544441470</pub-id></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Viuda-Martos</surname><given-names>M</given-names></name><name><surname>Fernández-Lóaez</surname><given-names>J</given-names></name><name><surname>Pérez-álvarez</surname><given-names>JA</given-names></name></person-group><article-title>Pomegranate and its many functional components as related to human health: a review</article-title><source><italic>Comprehensive Reviews in Food Science and Food Safety</italic></source><year>2010</year><volume>9</volume><issue>6</issue><fpage>635</fpage><lpage>654</lpage><pub-id pub-id-type="other">2-s2.0-79951776922</pub-id></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elfalleh</surname><given-names>W</given-names></name><name><surname>Hannachi</surname><given-names>H</given-names></name><name><surname>Tlili</surname><given-names>N</given-names></name><name><surname>Yahia</surname><given-names>Y</given-names></name><name><surname>Nasri</surname><given-names>N</given-names></name><name><surname>Ferchichi</surname><given-names>A</given-names></name></person-group><article-title>Total phenolic contents and antioxidant activities of pomegranate peel, seed, leaf and flower</article-title><source><italic>Journal of Medicinal Plants Research</italic></source><year>2012</year><volume>6</volume><issue>32</issue><fpage>4724</fpage><lpage>4730</lpage></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kohno</surname><given-names>H</given-names></name><name><surname>Suzuki</surname><given-names>R</given-names></name><name><surname>Yasui</surname><given-names>Y</given-names></name><name><surname>Hosokawa</surname><given-names>M</given-names></name><name><surname>Miyashita</surname><given-names>K</given-names></name><name><surname>Tanaka</surname><given-names>T</given-names></name></person-group><article-title>Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats</article-title><source><italic>Cancer Science</italic></source><year>2004</year><volume>95</volume><issue>6</issue><fpage>481</fpage><lpage>486</lpage><pub-id pub-id-type="other">2-s2.0-3042551491</pub-id><pub-id pub-id-type="pmid">15182427</pub-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lansky</surname><given-names>EP</given-names></name><name><surname>Newman</surname><given-names>RA</given-names></name></person-group><article-title><italic>Punica granatum</italic> (pomegranate) and its potential for prevention and treatment of inflammation and cancer</article-title><source><italic>Journal of Ethnopharmacology</italic></source><year>2007</year><volume>109</volume><issue>2</issue><fpage>177</fpage><lpage>206</lpage><pub-id pub-id-type="other">2-s2.0-33845602057</pub-id><pub-id pub-id-type="pmid">17157465</pub-id></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Monica</surname><given-names>V</given-names></name><name><surname>Raquel L Pinyi</surname><given-names>H</given-names></name><name><surname>Josep</surname><given-names>BR</given-names></name></person-group><article-title>Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents</article-title><source><italic>Evidence-Based Complementary and Alternative Medicine</italic></source><year>2013</year><volume>2013</volume><fpage>18 pages</fpage><pub-id pub-id-type="publisher-id">789764</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Elfalleh</surname><given-names>W</given-names></name><name><surname>Tlili</surname><given-names>N</given-names></name><name><surname>Nasri</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Antioxidant capacities of phenolic compounds and tocopherols from tunisian pomegranate (<italic>Punica granatum</italic>) fruits</article-title><source><italic>Journal of Food Science</italic></source><year>2011</year><volume>76</volume><issue>5</issue><fpage>C707</fpage><lpage>C713</lpage><pub-id pub-id-type="other">2-s2.0-79957899623</pub-id><pub-id pub-id-type="pmid">22417416</pub-id></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jain</surname><given-names>S</given-names></name><name><surname>Rai</surname><given-names>R</given-names></name><name><surname>Upadhyaya</surname><given-names>AR</given-names></name><name><surname>Malhotra</surname><given-names>G</given-names></name></person-group><article-title><italic>Punica granatum</italic>: a natural and recent approach towards dental problem</article-title><source><italic>International Journal of Pharmaceutical Sciences and Research</italic></source><year>2014</year><volume>2</volume><issue>1</issue><fpage>1</fpage><lpage>6</lpage></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seeram</surname><given-names>NP</given-names></name><name><surname>Nair</surname><given-names>MG</given-names></name></person-group><article-title>Inhibition of lipid peroxidation and structure-activity-related studies of the dietary constituents anthocyanins, anthocyanidins, and catechins</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2002</year><volume>50</volume><issue>19</issue><fpage>5308</fpage><lpage>5312</lpage><pub-id pub-id-type="other">2-s2.0-0037063411</pub-id><pub-id pub-id-type="pmid">12207466</pub-id></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amakura</surname><given-names>Y</given-names></name><name><surname>Okada</surname><given-names>M</given-names></name><name><surname>Tsuji</surname><given-names>S</given-names></name><name><surname>Tonogai</surname><given-names>Y</given-names></name></person-group><article-title>Determination of phenolic acids in fruit juices by isocratic column liquid chromatography</article-title><source><italic>Journal of Chromatography A</italic></source><year>2000</year><volume>891</volume><issue>1</issue><fpage>183</fpage><lpage>188</lpage><pub-id pub-id-type="other">2-s2.0-0034284217</pub-id><pub-id pub-id-type="pmid">10999637</pub-id></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tanaka</surname><given-names>T</given-names></name><name><surname>Nonaka</surname><given-names>G-I</given-names></name><name><surname>Nishioka</surname><given-names>I</given-names></name></person-group><article-title>Tannins and related compounds. XL. Revision of the structures of punicalin and punicalagin, and isolation and characterization of 2-O-galloylpunicalin from the bark of <italic>Punica granatum</italic> L</article-title><source><italic>Chemical and Pharmaceutical Bulletin</italic></source><year>1986</year><volume>34</volume><issue>2</issue><fpage>650</fpage><lpage>655</lpage><pub-id pub-id-type="other">2-s2.0-0022588256</pub-id></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gil</surname><given-names>MI</given-names></name><name><surname>Tomas-Barberan</surname><given-names>FA</given-names></name><name><surname>Hess-Pierce</surname><given-names>B</given-names></name><name><surname>Holcroft</surname><given-names>DM</given-names></name><name><surname>Kader</surname><given-names>AA</given-names></name></person-group><article-title>Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2000</year><volume>48</volume><issue>10</issue><fpage>4581</fpage><lpage>4589</lpage><pub-id pub-id-type="other">2-s2.0-0033788223</pub-id><pub-id pub-id-type="pmid">11052704</pub-id></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Neuhofer</surname><given-names>H</given-names></name><name><surname>Witte</surname><given-names>L</given-names></name><name><surname>Gorunovic</surname><given-names>M</given-names></name><name><surname>Czygan</surname><given-names>F-C</given-names></name></person-group><article-title>Alkaloids in the bark of <italic>Punica granatum</italic> L. (Pomegranate) from Yugoslavia</article-title><source><italic>Die Pharmazie</italic></source><year>1993</year><volume>48</volume><issue>5</issue><fpage>389</fpage><lpage>391</lpage><pub-id pub-id-type="other">2-s2.0-0027315037</pub-id></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vidal</surname><given-names>A</given-names></name><name><surname>Fallarero</surname><given-names>A</given-names></name><name><surname>Peña</surname><given-names>BR</given-names></name><etal></etal></person-group><article-title>Studies on the toxicity of <italic>Punica granatum</italic> L. (Punicaceae) whole fruit extracts</article-title><source><italic>Journal of Ethnopharmacology</italic></source><year>2003</year><volume>89</volume><issue>2-3</issue><fpage>295</fpage><lpage>300</lpage><pub-id pub-id-type="other">2-s2.0-0242721412</pub-id><pub-id pub-id-type="pmid">14611895</pub-id></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Elswijk</surname><given-names>DA</given-names></name><name><surname>Schobel</surname><given-names>UP</given-names></name><name><surname>Lansky</surname><given-names>EP</given-names></name><name><surname>Irth</surname><given-names>H</given-names></name><name><surname>van der Greef</surname><given-names>J</given-names></name></person-group><article-title>Rapid dereplication of estrogenic compounds in pomegranate (<italic>Punica granatum</italic>) using on-line biochemical detection coupled to mass spectrometry</article-title><source><italic>Phytochemistry</italic></source><year>2004</year><volume>65</volume><issue>2</issue><fpage>233</fpage><lpage>241</lpage><pub-id pub-id-type="other">2-s2.0-0742324892</pub-id><pub-id pub-id-type="pmid">14732284</pub-id></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Artik</surname><given-names>N</given-names></name><name><surname>Ceremroglu</surname><given-names>B</given-names></name><name><surname>Murakami</surname><given-names>H</given-names></name><name><surname>Mori</surname><given-names>T</given-names></name></person-group><article-title>Determination of phenolic compounds in pomegranate juice by using HPLC</article-title><source><italic>Fruit Processing</italic></source><year>1998</year><volume>8</volume><fpage>492</fpage><lpage>499</lpage></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cui</surname><given-names>S-M</given-names></name><name><surname>Sasada</surname><given-names>Y</given-names></name><name><surname>Sato</surname><given-names>H</given-names></name><name><surname>Nii</surname><given-names>N</given-names></name></person-group><article-title>Cell structure and sugar and acid contents in the arils of developing pomegranate fruit</article-title><source><italic>Journal of the Japanese Society for Horticultural Science</italic></source><year>2004</year><volume>73</volume><issue>3</issue><fpage>241</fpage><lpage>243</lpage><pub-id pub-id-type="other">2-s2.0-2942720853</pub-id></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Poyrazoğlu</surname><given-names>E</given-names></name><name><surname>Gökmen</surname><given-names>V</given-names></name><name><surname>Artik</surname><given-names>N</given-names></name></person-group><article-title>Organic acids and phenolic compounds in pomegranates (<italic>Punica granatum</italic> L.) grown in Turkey</article-title><source><italic>Journal of Food Composition and Analysis</italic></source><year>2002</year><volume>15</volume><issue>5</issue><fpage>567</fpage><lpage>575</lpage><pub-id pub-id-type="other">2-s2.0-0036771963</pub-id></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Du</surname><given-names>CT</given-names></name><name><surname>Wang</surname><given-names>PL</given-names></name><name><surname>Francis</surname><given-names>FJ</given-names></name></person-group><article-title>Anthocyanins of Pomegranate, <italic>Punica granatum</italic></article-title><source><italic>Journal of Food Science</italic></source><year>1975</year><volume>40</volume><issue>2</issue><fpage>417</fpage><lpage>418</lpage></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Waheed</surname><given-names>S</given-names></name><name><surname>Siddique</surname><given-names>N</given-names></name><name><surname>Rahman</surname><given-names>A</given-names></name><name><surname>Zaidi</surname><given-names>JH</given-names></name><name><surname>Ahmad</surname><given-names>S</given-names></name></person-group><article-title>INAA for dietary assessment of essential and other trace elements in fourteen fruits harvested and consumed in Pakistan</article-title><source><italic>Journal of Radioanalytical and Nuclear Chemistry</italic></source><year>2004</year><volume>260</volume><issue>3</issue><fpage>523</fpage><lpage>531</lpage><pub-id pub-id-type="other">2-s2.0-3542992691</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>THW</given-names></name><name><surname>Peng</surname><given-names>G</given-names></name><name><surname>Kota</surname><given-names>BP</given-names></name><etal></etal></person-group><article-title>Anti-diabetic action of <italic>Punica granatum</italic> flower extract: activation of PPAR-<italic>γ</italic> and identification of an active component</article-title><source><italic>Toxicology and Applied Pharmacology</italic></source><year>2005</year><volume>207</volume><issue>2</issue><fpage>160</fpage><lpage>169</lpage><pub-id pub-id-type="other">2-s2.0-23044467570</pub-id><pub-id pub-id-type="pmid">16102567</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Batta</surname><given-names>AK</given-names></name><name><surname>Rangaswami</surname><given-names>S</given-names></name></person-group><article-title>Crystalline chemical components of some vegetable drugs</article-title><source><italic>Phytochemistry</italic></source><year>1973</year><volume>12</volume><issue>1</issue><fpage>214</fpage><lpage>216</lpage></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lan</surname><given-names>J</given-names></name><name><surname>Lei</surname><given-names>F</given-names></name><name><surname>Hua</surname><given-names>L</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Xing</surname><given-names>D</given-names></name><name><surname>Du</surname><given-names>L</given-names></name></person-group><article-title>Transport behavior of ellagic acid of pomegranate leaf tannins and its correlation with total cholesterol alteration in HepG2 cells</article-title><source><italic>Biomedical Chromatography</italic></source><year>2009</year><volume>23</volume><issue>5</issue><fpage>531</fpage><lpage>536</lpage><pub-id pub-id-type="other">2-s2.0-67649646708</pub-id><pub-id pub-id-type="pmid">19101929</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chaitra</surname><given-names>RH</given-names></name><name><surname>Madhuri</surname><given-names>M</given-names></name><name><surname>Swaroop</surname><given-names>T</given-names></name><name><surname>Arijit</surname><given-names>D</given-names></name><name><surname>Sourav</surname><given-names>B</given-names></name><name><surname>Rohit</surname><given-names>KC</given-names></name></person-group><article-title>Evaluation of antimicrobial properties, phytochemical contents and antioxidant capacity of leaf extracts of <italic>Punica granatum</italic> L</article-title><source><italic>Journal of Biological Sciences</italic></source><year>2012</year><volume>1</volume><fpage>32</fpage><lpage>37</lpage></element-citation></ref><ref id="B35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nawwar</surname><given-names>MAM</given-names></name><name><surname>Hussein</surname><given-names>SAM</given-names></name><name><surname>Merfort</surname><given-names>I</given-names></name></person-group><article-title>Leaf phenolics of <italic>Punica granatum</italic></article-title><source><italic>Phytochemistry</italic></source><year>1994</year><volume>37</volume><issue>4</issue><fpage>1175</fpage><lpage>1177</lpage><pub-id pub-id-type="other">2-s2.0-0028028951</pub-id></element-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>R-F</given-names></name><name><surname>Xie</surname><given-names>W-D</given-names></name><name><surname>Zhang</surname><given-names>Z</given-names></name><etal></etal></person-group><article-title>Bioactive compounds from the seeds of <italic>Punica granatum</italic> (pomegranate)</article-title><source><italic>Journal of Natural Products</italic></source><year>2004</year><volume>67</volume><issue>12</issue><fpage>2096</fpage><lpage>2098</lpage><pub-id pub-id-type="other">2-s2.0-11844273249</pub-id><pub-id pub-id-type="pmid">15620261</pub-id></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schubert</surname><given-names>SY</given-names></name><name><surname>Lansky</surname><given-names>EP</given-names></name><name><surname>Neeman</surname><given-names>I</given-names></name></person-group><article-title>Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids</article-title><source><italic>Journal of Ethnopharmacology</italic></source><year>1999</year><volume>66</volume><issue>1</issue><fpage>11</fpage><lpage>17</lpage><pub-id pub-id-type="other">2-s2.0-0032976772</pub-id><pub-id pub-id-type="pmid">10432202</pub-id></element-citation></ref><ref id="B38"><label>38</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hornung</surname><given-names>E</given-names></name><name><surname>Pernstich</surname><given-names>C</given-names></name><name><surname>Feussner</surname><given-names>I</given-names></name></person-group><article-title>Formation of conjugated Δ11 Δ13-double bonds by Δ12-linoleic acid (1,4)-acyl-lipid-desaturase in pomegranate seeds</article-title><source><italic>European Journal of Biochemistry</italic></source><year>2002</year><volume>269</volume><issue>19</issue><fpage>4852</fpage><lpage>4859</lpage><pub-id pub-id-type="other">2-s2.0-0036025220</pub-id><pub-id pub-id-type="pmid">12354116</pub-id></element-citation></ref><ref id="B39"><label>39</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abd El Wahab</surname><given-names>SM</given-names></name><name><surname>El Fiki</surname><given-names>NM</given-names></name><name><surname>Mostafa</surname><given-names>SF</given-names></name><name><surname>Hassan</surname><given-names>AEB</given-names></name></person-group><article-title>Characterization of certain steroid hormones in <italic>Punica granatum</italic> L. seeds</article-title><source><italic>Bulletin of the Faculty of Pharmacy</italic></source><year>1998</year><volume>36</volume><fpage>11</fpage><lpage>15</lpage></element-citation></ref><ref id="B40"><label>40</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>ND</given-names></name><name><surname>Mehta</surname><given-names>R</given-names></name><name><surname>Yu</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Chemopreventive and adjuvant therapeutic potential of pomegranate (<italic>Punica granatum</italic>) for human breast cancer</article-title><source><italic>Breast Cancer Research and Treatment</italic></source><year>2002</year><volume>71</volume><issue>3</issue><fpage>203</fpage><lpage>217</lpage><pub-id pub-id-type="other">2-s2.0-0036201937</pub-id><pub-id pub-id-type="pmid">12002340</pub-id></element-citation></ref><ref id="B41"><label>41</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lansky</surname><given-names>EP</given-names></name><name><surname>Jiang</surname><given-names>W</given-names></name><name><surname>Mo</surname><given-names>H</given-names></name><etal></etal></person-group><article-title>Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions</article-title><source><italic>Investigational New Drugs</italic></source><year>2005</year><volume>23</volume><issue>1</issue><fpage>11</fpage><lpage>20</lpage><pub-id pub-id-type="other">2-s2.0-8744253746</pub-id><pub-id pub-id-type="pmid">15528976</pub-id></element-citation></ref><ref id="B42"><label>42</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jurenka</surname><given-names>J</given-names></name></person-group><article-title>Therapeutic applications of pomegranate (<italic>Punica granatum</italic> L.): a review</article-title><source><italic>Alternative Medicine Review</italic></source><year>2008</year><volume>13</volume><issue>2</issue><fpage>128</fpage><lpage>144</lpage><pub-id pub-id-type="other">2-s2.0-47549111139</pub-id><pub-id pub-id-type="pmid">18590349</pub-id></element-citation></ref><ref id="B43"><label>43</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Neurath</surname><given-names>AR</given-names></name><name><surname>Strick</surname><given-names>N</given-names></name><name><surname>Li</surname><given-names>Y-Y</given-names></name><name><surname>Debnath</surname><given-names>AK</given-names></name></person-group><article-title><italic>Punica granatum</italic> (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide</article-title><source><italic>BMC Infectious Diseases</italic></source><year>2004</year><volume>4, article 41</volume><pub-id pub-id-type="other">2-s2.0-10144220702</pub-id></element-citation></ref><ref id="B44"><label>44</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toi</surname><given-names>M</given-names></name><name><surname>Bando</surname><given-names>H</given-names></name><name><surname>Ramachandran</surname><given-names>C</given-names></name><etal></etal></person-group><article-title>Preliminary studies on the anti-angiogenic potential of pomegranate fractions <italic>in vitro</italic> and <italic>in vivo</italic></article-title><source><italic>Angiogenesis</italic></source><year>2003</year><volume>6</volume><issue>2</issue><fpage>121</fpage><lpage>128</lpage><pub-id pub-id-type="other">2-s2.0-0842333242</pub-id><pub-id pub-id-type="pmid">14739618</pub-id></element-citation></ref><ref id="B45"><label>45</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mehta</surname><given-names>R</given-names></name><name><surname>Lansky</surname><given-names>EP</given-names></name></person-group><article-title>Breast cancer chemopreventive properties of pomegranate (<italic>Punica granatum</italic>) fruit extracts in a mouse mammary organ culture</article-title><source><italic>European Journal of Cancer Prevention</italic></source><year>2004</year><volume>13</volume><issue>4</issue><fpage>345</fpage><lpage>348</lpage><pub-id pub-id-type="other">2-s2.0-4143152009</pub-id><pub-id pub-id-type="pmid">15554563</pub-id></element-citation></ref><ref id="B46"><label>46</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jeune</surname><given-names>MAL</given-names></name><name><surname>Kumi-Diaka</surname><given-names>J</given-names></name><name><surname>Brown</surname><given-names>J</given-names></name></person-group><article-title>Anticancer activities of pomegranate extracts and genistein in human breast cancer cells</article-title><source><italic>Journal of Medicinal Food</italic></source><year>2005</year><volume>8</volume><issue>4</issue><fpage>469</fpage><lpage>475</lpage><pub-id pub-id-type="other">2-s2.0-31044452188</pub-id><pub-id pub-id-type="pmid">16379557</pub-id></element-citation></ref><ref id="B47"><label>47</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Faria</surname><given-names>A</given-names></name><name><surname>Conceição</surname><given-names>C</given-names></name></person-group><article-title>The bioactivity of pomegranate: impact on health and disease</article-title><source><italic>Critical Reviews in Food Science and Nutrition</italic></source><year>2011</year><volume>51</volume><issue>7</issue><fpage>626</fpage><lpage>634</lpage><pub-id pub-id-type="other">2-s2.0-79960859812</pub-id><pub-id pub-id-type="pmid">21793725</pub-id></element-citation></ref><ref id="B48"><label>48</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Alcon</surname><given-names>A</given-names></name><name><surname>Yuan</surname><given-names>H</given-names></name><name><surname>Ho</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>Q-J</given-names></name><name><surname>Martins-Green</surname><given-names>M</given-names></name></person-group><article-title>Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells</article-title><source><italic>Integrative Biology</italic></source><year>2011</year><volume>3</volume><issue>7</issue><fpage>742</fpage><lpage>754</lpage><pub-id pub-id-type="other">2-s2.0-79959975747</pub-id><pub-id pub-id-type="pmid">21594291</pub-id></element-citation></ref><ref id="B49"><label>49</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Burton</surname><given-names>A</given-names></name></person-group><article-title>Chemoprevention: eat ginger, rub on pomegranate</article-title><source><italic>The Lancet Oncology</italic></source><year>2003</year><volume>4</volume><issue>12</issue><fpage>p. 715</fpage><pub-id pub-id-type="other">2-s2.0-0347503595</pub-id></element-citation></ref><ref id="B50"><label>50</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adhami</surname><given-names>VM</given-names></name><name><surname>Siddiqui</surname><given-names>IA</given-names></name><name><surname>Syed</surname><given-names>DN</given-names></name><name><surname>Lall</surname><given-names>RK</given-names></name><name><surname>Mukhtar</surname><given-names>H</given-names></name></person-group><article-title>Oral infusion of pomegranate fruit extract inhibits prostate carcinogenesis in the TRAMP model</article-title><source><italic>Carcinogenesis</italic></source><year>2012</year><volume>33</volume><issue>3</issue><fpage>644</fpage><lpage>651</lpage><pub-id pub-id-type="other">2-s2.0-84857949057</pub-id><pub-id pub-id-type="pmid">22198212</pub-id></element-citation></ref><ref id="B51"><label>51</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Herszényi</surname><given-names>L</given-names></name><name><surname>Hritz</surname><given-names>I</given-names></name><name><surname>Lakatos</surname><given-names>G</given-names></name><name><surname>Varga</surname><given-names>MZ</given-names></name><name><surname>Tulassay</surname><given-names>Z</given-names></name></person-group><article-title>The behavior of matrix metalloproteinases and their inhibitors in colorectal cancer</article-title><source><italic>International Journal of Molecular Sciences</italic></source><year>2012</year><volume>13</volume><issue>10</issue><fpage>13240</fpage><lpage>13263</lpage><pub-id pub-id-type="pmid">23202950</pub-id></element-citation></ref><ref id="B52"><label>52</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sarkar</surname><given-names>FH</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>Z</given-names></name><name><surname>Kong</surname><given-names>D</given-names></name></person-group><article-title>Cellular signaling perturbation by natural products</article-title><source><italic>Cellular Signalling</italic></source><year>2009</year><volume>21</volume><issue>11</issue><fpage>1541</fpage><lpage>1547</lpage><pub-id pub-id-type="other">2-s2.0-69049087664</pub-id><pub-id pub-id-type="pmid">19298854</pub-id></element-citation></ref><ref id="B53"><label>53</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sreeja</surname><given-names>S</given-names></name><name><surname>Santhosh Kumar</surname><given-names>TR</given-names></name><name><surname>Lakshmi</surname><given-names>BS</given-names></name><name><surname>Sreeja</surname><given-names>S</given-names></name></person-group><article-title>Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and <italic>in vivo</italic> models of estrogen deprivation</article-title><source><italic>The Journal of Nutritional Biochemistry</italic></source><year>2012</year><volume>23</volume><issue>7</issue><fpage>725</fpage><lpage>732</lpage><pub-id pub-id-type="other">2-s2.0-79961138407</pub-id><pub-id pub-id-type="pmid">21839626</pub-id></element-citation></ref><ref id="B54"><label>54</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Etique</surname><given-names>N</given-names></name><name><surname>Grillier-Vuissoz</surname><given-names>I</given-names></name><name><surname>Flament</surname><given-names>S</given-names></name></person-group><article-title>Ethanol stimulates the secretion of matrix metalloproteinases 2 and 9 in MCF-7 human breast cancer cells</article-title><source><italic>Oncology Reports</italic></source><year>2006</year><volume>15</volume><issue>3</issue><fpage>603</fpage><lpage>608</lpage><pub-id pub-id-type="other">2-s2.0-33645743712</pub-id><pub-id pub-id-type="pmid">16465419</pub-id></element-citation></ref><ref id="B55"><label>55</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Afaq</surname><given-names>F</given-names></name><name><surname>Malik</surname><given-names>A</given-names></name><name><surname>Syed</surname><given-names>D</given-names></name><name><surname>Maes</surname><given-names>D</given-names></name><name><surname>Matsui</surname><given-names>MS</given-names></name><name><surname>Mukhtar</surname><given-names>H</given-names></name></person-group><article-title>Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes</article-title><source><italic>Photochemistry and Photobiology</italic></source><year>2005</year><volume>81</volume><issue>1</issue><fpage>38</fpage><lpage>45</lpage><pub-id pub-id-type="other">2-s2.0-14744277141</pub-id><pub-id pub-id-type="pmid">15493960</pub-id></element-citation></ref><ref id="B56"><label>56</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Adams</surname><given-names>LS</given-names></name><name><surname>Seeram</surname><given-names>NP</given-names></name><name><surname>Aggarwal</surname><given-names>BB</given-names></name><name><surname>Takada</surname><given-names>Y</given-names></name><name><surname>Sand</surname><given-names>D</given-names></name><name><surname>Heber</surname><given-names>D</given-names></name></person-group><article-title>Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2006</year><volume>54</volume><issue>3</issue><fpage>980</fpage><lpage>985</lpage><pub-id pub-id-type="other">2-s2.0-33244454723</pub-id><pub-id pub-id-type="pmid">16448212</pub-id></element-citation></ref><ref id="B57"><label>57</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Koyama</surname><given-names>S</given-names></name><name><surname>Cobb</surname><given-names>LJ</given-names></name><name><surname>Mehta</surname><given-names>HH</given-names></name><etal></etal></person-group><article-title>Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis</article-title><source><italic>Growth Hormone and IGF Research</italic></source><year>2010</year><volume>20</volume><issue>1</issue><fpage>55</fpage><lpage>62</lpage><pub-id pub-id-type="other">2-s2.0-74649084016</pub-id><pub-id pub-id-type="pmid">19853487</pub-id></element-citation></ref><ref id="B58"><label>58</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fuhrman</surname><given-names>B</given-names></name><name><surname>Volkova</surname><given-names>N</given-names></name><name><surname>Aviram</surname><given-names>M</given-names></name></person-group><article-title>Pomegranate juice polyphenols increase recombinant paraoxonase-1 binding to high-density lipoprotein: studies <italic>in vitro</italic> and in diabetic patients</article-title><source><italic>Nutrition</italic></source><year>2010</year><volume>26</volume><issue>4</issue><fpage>359</fpage><lpage>366</lpage><pub-id pub-id-type="other">2-s2.0-77349101573</pub-id><pub-id pub-id-type="pmid">19762215</pub-id></element-citation></ref><ref id="B59"><label>59</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Nigris</surname><given-names>F</given-names></name><name><surname>Williams-Ignarro</surname><given-names>S</given-names></name><name><surname>Lerman</surname><given-names>LO</given-names></name><etal></etal></person-group><article-title>Beneficial effects of pomegranate juice on oxidation-sensitive genes and endothelial nitric oxide synthase activity at sites of perturbed shear stress</article-title><source><italic>Proceedings of the National Academy of Sciences of the United States of America</italic></source><year>2005</year><volume>102</volume><issue>13</issue><fpage>4896</fpage><lpage>4901</lpage><pub-id pub-id-type="other">2-s2.0-20144388620</pub-id><pub-id pub-id-type="pmid">15781875</pub-id></element-citation></ref><ref id="B60"><label>60</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aviram</surname><given-names>M</given-names></name><name><surname>Rosenblat</surname><given-names>M</given-names></name><name><surname>Gaitini</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation</article-title><source><italic>Clinical Nutrition</italic></source><year>2004</year><volume>23</volume><issue>3</issue><fpage>423</fpage><lpage>433</lpage><pub-id pub-id-type="other">2-s2.0-3042653405</pub-id><pub-id pub-id-type="pmid">15158307</pub-id></element-citation></ref><ref id="B61"><label>61</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Azadzoi</surname><given-names>KM</given-names></name><name><surname>Schulman</surname><given-names>RN</given-names></name><name><surname>Aviram</surname><given-names>M</given-names></name><name><surname>Siroky</surname><given-names>MB</given-names></name></person-group><article-title>Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants</article-title><source><italic>The Journal of Urology</italic></source><year>2005</year><volume>174</volume><issue>1</issue><fpage>386</fpage><lpage>393</lpage><pub-id pub-id-type="other">2-s2.0-20444461230</pub-id><pub-id pub-id-type="pmid">15947695</pub-id></element-citation></ref><ref id="B62"><label>62</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Esmaillzadeh</surname><given-names>A</given-names></name><name><surname>Tahbaz</surname><given-names>F</given-names></name><name><surname>Gaieni</surname><given-names>I</given-names></name><name><surname>Alavi-Majd</surname><given-names>H</given-names></name><name><surname>Azadbakht</surname><given-names>L</given-names></name></person-group><article-title>Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia</article-title><source><italic>International Journal for Vitamin and Nutrition Research</italic></source><year>2006</year><volume>76</volume><issue>3</issue><fpage>147</fpage><lpage>151</lpage><pub-id pub-id-type="other">2-s2.0-33750496423</pub-id><pub-id pub-id-type="pmid">17048194</pub-id></element-citation></ref><ref id="B63"><label>63</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aviram</surname><given-names>M</given-names></name><name><surname>Volkova</surname><given-names>N</given-names></name><name><surname>Coleman</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies <italic>in vivo</italic> in atherosclerotic apolipoprotein E-deficient (E°) mice and <italic>in vitro</italic> in cultured macrophages and lipoproteins</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2008</year><volume>56</volume><issue>3</issue><fpage>1148</fpage><lpage>1157</lpage><pub-id pub-id-type="other">2-s2.0-80051855181</pub-id><pub-id pub-id-type="pmid">18173244</pub-id></element-citation></ref><ref id="B64"><label>64</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jordan</surname><given-names>VC</given-names></name><name><surname>Phelps</surname><given-names>E</given-names></name><name><surname>Lindgren</surname><given-names>JU</given-names></name></person-group><article-title>Effects of anti-estrogens on bone in castrated and intact female rats</article-title><source><italic>Breast Cancer Research and Treatment</italic></source><year>1987</year><volume>10</volume><issue>1</issue><fpage>31</fpage><lpage>35</lpage><pub-id pub-id-type="other">2-s2.0-0023547257</pub-id><pub-id pub-id-type="pmid">3689979</pub-id></element-citation></ref><ref id="B65"><label>65</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ke</surname><given-names>HZ</given-names></name><name><surname>Paralkak</surname><given-names>VM</given-names></name><name><surname>Grasser</surname><given-names>WA</given-names></name><etal></etal></person-group><article-title>Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus, and body composition in rat models</article-title><source><italic>Endocrinology</italic></source><year>1998</year><volume>139</volume><issue>4</issue><fpage>2068</fpage><lpage>2076</lpage><pub-id pub-id-type="other">2-s2.0-0001236520</pub-id><pub-id pub-id-type="pmid">9528995</pub-id></element-citation></ref><ref id="B66"><label>66</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lerner</surname><given-names>LJ</given-names></name><name><surname>Jordan</surname><given-names>VC</given-names></name></person-group><article-title>Development of antiestrogens and their use in breast cancer: eighth cain memorial award lecture</article-title><source><italic>Cancer Research</italic></source><year>1990</year><volume>50</volume><issue>14</issue><fpage>4177</fpage><lpage>4189</lpage><pub-id pub-id-type="other">2-s2.0-0025338591</pub-id><pub-id pub-id-type="pmid">2194650</pub-id></element-citation></ref><ref id="B67"><label>67</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Banu</surname><given-names>J</given-names></name></person-group><article-title>The ovariectomized mice and rats</article-title><source><italic>Osteoporosis Research</italic></source><year>2011</year><publisher-name>SpringerLondon</publisher-name></element-citation></ref><ref id="B68"><label>68</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Sreekumar</surname><given-names>S</given-names></name></person-group><source><italic>Selective estrogen receptor modulator (SERM) activity of Pomegranate (<italic>Punica granatum</italic> L.): implications for estrogen dependant breast cancer [dissertation]</italic></source><year>2011</year><publisher-name>University of Kerala</publisher-name></element-citation></ref><ref id="B69"><label>69</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y-Y</given-names></name><name><surname>Kim</surname><given-names>S-H</given-names></name><name><surname>Oh</surname><given-names>S</given-names></name><etal></etal></person-group><article-title>Increased fat due to estrogen deficiency induces bone loss by elevating monocyte chemoattractant protein-1 (MCP-1) production</article-title><source><italic>Molecules and Cells</italic></source><year>2010</year><volume>29</volume><issue>3</issue><fpage>277</fpage><lpage>282</lpage><pub-id pub-id-type="other">2-s2.0-77953542456</pub-id><pub-id pub-id-type="pmid">20108169</pub-id></element-citation></ref><ref id="B70"><label>70</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Neerup</surname><given-names>TSR</given-names></name><name><surname>Stahlhut</surname><given-names>M</given-names></name><name><surname>Petersen</surname><given-names>JS</given-names></name><etal></etal></person-group><article-title>ZP2307, a novel, cyclic PTH(1-17) analog that augments bone mass in ovariectomized rats</article-title><source><italic>Bone</italic></source><year>2011</year><volume>48</volume><issue>6</issue><fpage>1319</fpage><lpage>1327</lpage><pub-id pub-id-type="other">2-s2.0-79955916568</pub-id><pub-id pub-id-type="pmid">21376152</pub-id></element-citation></ref><ref id="B71"><label>71</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>H</given-names></name><name><surname>Tranguch</surname><given-names>S</given-names></name><name><surname>Xie</surname><given-names>H</given-names></name><name><surname>Hanley</surname><given-names>G</given-names></name><name><surname>Das</surname><given-names>SK</given-names></name><name><surname>Dey</surname><given-names>SK</given-names></name></person-group><article-title>Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus</article-title><source><italic>Proceedings of the National Academy of Sciences of the United States of America</italic></source><year>2005</year><volume>102</volume><issue>28</issue><fpage>9960</fpage><lpage>9965</lpage><pub-id pub-id-type="other">2-s2.0-22244456759</pub-id><pub-id pub-id-type="pmid">15987781</pub-id></element-citation></ref><ref id="B72"><label>72</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Amini</surname><given-names>AA</given-names></name><name><surname>Nair</surname><given-names>LS</given-names></name></person-group><article-title>Lactoferrin: a biologically active molecule for bone regeneration</article-title><source><italic>Current Medicinal Chemistry</italic></source><year>2011</year><volume>18</volume><issue>8</issue><fpage>1220</fpage><lpage>1229</lpage><pub-id pub-id-type="other">2-s2.0-79952784789</pub-id><pub-id pub-id-type="pmid">21291364</pub-id></element-citation></ref><ref id="B73"><label>73</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ignarro</surname><given-names>LJ</given-names></name><name><surname>Byrns</surname><given-names>RE</given-names></name><name><surname>Sumi</surname><given-names>D</given-names></name><name><surname>de Nigris</surname><given-names>F</given-names></name><name><surname>Napoli</surname><given-names>C</given-names></name></person-group><article-title>Pomegranate juice protects nitric oxide against oxidative destruction and enhances the biological actions of nitric oxide</article-title><source><italic>Nitric Oxide: Biology and Chemistry</italic></source><year>2006</year><volume>15</volume><issue>2</issue><fpage>93</fpage><lpage>102</lpage><pub-id pub-id-type="other">2-s2.0-33746795022</pub-id></element-citation></ref><ref id="B74"><label>74</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Parmar</surname><given-names>HS</given-names></name><name><surname>Kar</surname><given-names>A</given-names></name></person-group><article-title>Medicinal values of fruit peels from Citrus sinensis, <italic>Punica granatum</italic>, and Musa paradisiaca with respect to alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones</article-title><source><italic>Journal of Medicinal Food</italic></source><year>2008</year><volume>11</volume><issue>2</issue><fpage>376</fpage><lpage>381</lpage><pub-id pub-id-type="other">2-s2.0-46749094645</pub-id><pub-id pub-id-type="pmid">18598183</pub-id></element-citation></ref><ref id="B75"><label>75</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Toklu</surname><given-names>HZ</given-names></name><name><surname>Dumlu</surname><given-names>MU</given-names></name><name><surname>Sehirli</surname><given-names>Ö</given-names></name><etal></etal></person-group><article-title>Pomegranate peel extract prevents liver fibrosis in biliary-obstructed rats</article-title><source><italic>Journal of Pharmacy and Pharmacology</italic></source><year>2007</year><volume>59</volume><issue>9</issue><fpage>1287</fpage><lpage>1295</lpage><pub-id pub-id-type="other">2-s2.0-34548455462</pub-id><pub-id pub-id-type="pmid">17939210</pub-id></element-citation></ref><ref id="B76"><label>76</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chidambara Murthy</surname><given-names>MKN</given-names></name><name><surname>Jayaprakasha</surname><given-names>GK</given-names></name><name><surname>Singh</surname><given-names>RP</given-names></name></person-group><article-title>Studies on antioxidant activity of pomegranate (<italic>Punica granatum</italic>) peel extract using <italic>in vivo</italic> models</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2002</year><volume>50</volume><issue>17</issue><fpage>4791</fpage><lpage>4795</lpage><pub-id pub-id-type="other">2-s2.0-0037077407</pub-id><pub-id pub-id-type="pmid">12166961</pub-id></element-citation></ref><ref id="B77"><label>77</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shukla</surname><given-names>M</given-names></name><name><surname>Gupta</surname><given-names>K</given-names></name><name><surname>Rasheed</surname><given-names>Z</given-names></name><name><surname>Khan</surname><given-names>KA</given-names></name><name><surname>Haqqi</surname><given-names>TM</given-names></name></person-group><article-title>Consumption of hydrolyzable tannins-rich pomegranate extract suppresses inflammation and joint damage in rheumatoid arthritis</article-title><source><italic>Nutrition</italic></source><year>2008</year><volume>24</volume><issue>7-8</issue><fpage>733</fpage><lpage>743</lpage><pub-id pub-id-type="other">2-s2.0-44749083500</pub-id><pub-id pub-id-type="pmid">18490140</pub-id></element-citation></ref><ref id="B78"><label>78</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Larrosa</surname><given-names>M</given-names></name><name><surname>González-Sarrías</surname><given-names>A</given-names></name><name><surname>Yáñez-Gascón</surname><given-names>MJ</given-names></name><etal></etal></person-group><article-title>Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism</article-title><source><italic>The Journal of Nutritional Biochemistry</italic></source><year>2010</year><volume>21</volume><issue>8</issue><fpage>717</fpage><lpage>725</lpage><pub-id pub-id-type="other">2-s2.0-77954657360</pub-id><pub-id pub-id-type="pmid">19616930</pub-id></element-citation></ref><ref id="B79"><label>79</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>C-J</given-names></name><name><surname>Chen</surname><given-names>L-G</given-names></name><name><surname>Liang</surname><given-names>W-L</given-names></name><name><surname>Wang</surname><given-names>C-C</given-names></name></person-group><article-title>Anti-inflammatory effects of <italic>Punica granatum</italic> Linne <italic>in vitro</italic> and <italic>in vivo</italic></article-title><source><italic>Food Chemistry</italic></source><year>2010</year><volume>118</volume><issue>2</issue><fpage>315</fpage><lpage>322</lpage><pub-id pub-id-type="other">2-s2.0-69049107412</pub-id></element-citation></ref><ref id="B80"><label>80</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rasheed</surname><given-names>Z</given-names></name><name><surname>Akhtar</surname><given-names>N</given-names></name><name><surname>Anbazhagan</surname><given-names>AN</given-names></name><name><surname>Ramamurthy</surname><given-names>S</given-names></name><name><surname>Shukla</surname><given-names>M</given-names></name><name><surname>Haqqi</surname><given-names>TM</given-names></name></person-group><article-title>Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP kinases and NF-<italic>κ</italic>B in human KU812 cells</article-title><source><italic>Journal of Inflammation</italic></source><year>2009</year><volume>6, article 1</volume><pub-id pub-id-type="other">2-s2.0-61849149335</pub-id></element-citation></ref><ref id="B81"><label>81</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Menezes</surname><given-names>SMS</given-names></name><name><surname>Cordeiro</surname><given-names>LN</given-names></name><name><surname>Viana</surname><given-names>GSB</given-names></name></person-group><article-title><italic>Punica granatum</italic> (pomegranate) extract is active against dental plaque</article-title><source><italic>Journal of Herbal Pharmacotherapy</italic></source><year>2006</year><volume>6</volume><issue>2</issue><fpage>79</fpage><lpage>92</lpage><pub-id pub-id-type="other">2-s2.0-33845711624</pub-id><pub-id pub-id-type="pmid">17182487</pub-id></element-citation></ref><ref id="B82"><label>82</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Souza Vasconcelos</surname><given-names>LC</given-names></name><name><surname>Correia Sampaio</surname><given-names>MC</given-names></name><name><surname>Correia Sampaio</surname><given-names>F</given-names></name><name><surname>Higino</surname><given-names>JS</given-names></name></person-group><article-title>Use of <italic>Punica granatum</italic> as an antifungal agent against candidosis associated with denture stomatitis</article-title><source><italic>Mycoses</italic></source><year>2003</year><volume>46</volume><issue>5-6</issue><fpage>192</fpage><lpage>196</lpage><pub-id pub-id-type="other">2-s2.0-0038391250</pub-id><pub-id pub-id-type="pmid">12801361</pub-id></element-citation></ref><ref id="B83"><label>83</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ewies</surname><given-names>AAA</given-names></name></person-group><article-title>Phytoestrogens in the management of the menopause: up-to-date</article-title><source><italic>Obstetrical and Gynecological Survey</italic></source><year>2002</year><volume>57</volume><issue>5</issue><fpage>306</fpage><lpage>313</lpage><pub-id pub-id-type="other">2-s2.0-0036245076</pub-id><pub-id pub-id-type="pmid">11997677</pub-id></element-citation></ref><ref id="B84"><label>84</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>J-Y</given-names></name><name><surname>Aizawa</surname><given-names>T</given-names></name></person-group><article-title>Quantitative structure-activity relationships for estrogen receptor binding affinity of phenolic chemicals</article-title><source><italic>Water Research</italic></source><year>2003</year><volume>37</volume><issue>6</issue><fpage>1213</fpage><lpage>1222</lpage><pub-id pub-id-type="other">2-s2.0-0037332610</pub-id><pub-id pub-id-type="pmid">12598185</pub-id></element-citation></ref><ref id="B85"><label>85</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Setchell</surname><given-names>KDR</given-names></name></person-group><article-title>Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones</article-title><source><italic>American Journal of Clinical Nutrition</italic></source><year>1998</year><volume>68</volume><issue>6</issue><fpage>1333S</fpage><lpage>1346S</lpage><pub-id pub-id-type="other">2-s2.0-0031741906</pub-id><pub-id pub-id-type="pmid">9848496</pub-id></element-citation></ref><ref id="B86"><label>86</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anderson</surname><given-names>JJB</given-names></name><name><surname>Anthony</surname><given-names>M</given-names></name><name><surname>Messina</surname><given-names>M</given-names></name><name><surname>Garner</surname><given-names>SC</given-names></name></person-group><article-title>Effects of phyto-oestrogens on tissues</article-title><source><italic>Nutrition Research Reviews</italic></source><year>1999</year><volume>12</volume><issue>1</issue><fpage>75</fpage><lpage>116</lpage><pub-id pub-id-type="other">2-s2.0-0032817379</pub-id><pub-id pub-id-type="pmid">19087447</pub-id></element-citation></ref><ref id="B87"><label>87</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shang</surname><given-names>Y</given-names></name><name><surname>Brown</surname><given-names>M</given-names></name></person-group><article-title>Molecular determinants for the tissue specificity of SERMs</article-title><source><italic>Science</italic></source><year>2002</year><volume>295</volume><issue>5564</issue><fpage>2465</fpage><lpage>2468</lpage><pub-id pub-id-type="other">2-s2.0-0037192501</pub-id><pub-id pub-id-type="pmid">11923541</pub-id></element-citation></ref><ref id="B88"><label>88</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yao</surname><given-names>K</given-names></name><name><surname>Jordan</surname><given-names>VC</given-names></name></person-group><article-title>Questions about tamoxifen and the future use of antiestrogens</article-title><source><italic>Oncologist</italic></source><year>1998</year><volume>3</volume><issue>2</issue><fpage>104</fpage><lpage>110</lpage><pub-id pub-id-type="other">2-s2.0-0031923550</pub-id><pub-id pub-id-type="pmid">10388091</pub-id></element-citation></ref><ref id="B89"><label>89</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fisher</surname><given-names>B</given-names></name><name><surname>Dignam</surname><given-names>J</given-names></name><name><surname>Bryant</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors</article-title><source><italic>Journal of the National Cancer Institute</italic></source><year>1996</year><volume>88</volume><issue>21</issue><fpage>1529</fpage><lpage>1542</lpage><pub-id pub-id-type="other">2-s2.0-10344238569</pub-id><pub-id pub-id-type="pmid">8901851</pub-id></element-citation></ref><ref id="B90"><label>90</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cortesi</surname><given-names>L</given-names></name><name><surname>de Matteis</surname><given-names>E</given-names></name><name><surname>Rashid</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Distribution of second primary malignancies suggests a bidirectional effect between breast and endometrial cancer a population-based study</article-title><source><italic>International Journal of Gynecological Cancer</italic></source><year>2009</year><volume>19</volume><issue>8</issue><fpage>1358</fpage><lpage>1363</lpage><pub-id pub-id-type="other">2-s2.0-73349136762</pub-id><pub-id pub-id-type="pmid">20009890</pub-id></element-citation></ref><ref id="B91"><label>91</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maru</surname><given-names>I</given-names></name><name><surname>Ohnishi</surname><given-names>J</given-names></name><name><surname>Yamaguchi</surname><given-names>S</given-names></name><name><surname>Oda</surname><given-names>Y</given-names></name><name><surname>Kakehi</surname><given-names>K</given-names></name><name><surname>Ohta</surname><given-names>Y</given-names></name></person-group><article-title>An estrogen-like activity in pomegranate juice</article-title><source><italic>Journal of the Japanese Society For Food Science and Technology</italic></source><year>2001</year><volume>48</volume><issue>2</issue><fpage>146</fpage><lpage>149</lpage></element-citation></ref><ref id="B92"><label>92</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Brower</surname><given-names>V</given-names></name></person-group><article-title>Nutraceuticals: poised for a healthy slice of the healthcare market?</article-title><source><italic>Nature Biotechnology</italic></source><year>1998</year><volume>16</volume><issue>8</issue><fpage>728</fpage><lpage>730</lpage><pub-id pub-id-type="other">2-s2.0-0031928015</pub-id></element-citation></ref><ref id="B93"><label>93</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malik</surname><given-names>A</given-names></name></person-group><article-title>The potentials of nutraceuticals</article-title><source><italic>Pharmainfo.net</italic></source><year>2008</year><volume>6</volume></element-citation></ref><ref id="B94"><label>94</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dureja</surname><given-names>H</given-names></name><name><surname>Kaushik</surname><given-names>D</given-names></name><name><surname>Kumar</surname><given-names>V</given-names></name></person-group><article-title>Developments in nutraceuticals</article-title><source><italic>Indian Journal of Pharmacology</italic></source><year>2003</year><volume>35</volume><issue>6</issue><fpage>363</fpage><lpage>372</lpage><pub-id pub-id-type="other">2-s2.0-0344234440</pub-id></element-citation></ref><ref id="B95"><label>95</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tezcan</surname><given-names>F</given-names></name><name><surname>Gültekin-Özgüven</surname><given-names>M</given-names></name><name><surname>Diken</surname><given-names>T</given-names></name><name><surname>Özçelik</surname><given-names>B</given-names></name><name><surname>Erim</surname><given-names>FB</given-names></name></person-group><article-title>Antioxidant activity and total phenolic, organic acid and sugar content in commercial pomegranate juices</article-title><source><italic>Food Chemistry</italic></source><year>2009</year><volume>115</volume><issue>3</issue><fpage>873</fpage><lpage>877</lpage><pub-id pub-id-type="other">2-s2.0-62249219791</pub-id></element-citation></ref><ref id="B96"><label>96</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Guo</surname><given-names>C</given-names></name><name><surname>Yang</surname><given-names>J</given-names></name><name><surname>Wei</surname><given-names>J</given-names></name><name><surname>Xu</surname><given-names>J</given-names></name><name><surname>Cheng</surname><given-names>S</given-names></name></person-group><article-title>Evaluation of antioxidant properties of pomegranate peel extract in comparison with pomegranate pulp extract</article-title><source><italic>Food Chemistry</italic></source><year>2006</year><volume>96</volume><issue>2</issue><fpage>254</fpage><lpage>260</lpage><pub-id pub-id-type="other">2-s2.0-27644593437</pub-id></element-citation></ref><ref id="B97"><label>97</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mirdehghan</surname><given-names>SH</given-names></name><name><surname>Rahemi</surname><given-names>M</given-names></name></person-group><article-title>Seasonal changes of mineral nutrients and phenolics in pomegranate (<italic>Punica granatum</italic> L.) fruit</article-title><source><italic>Scientia Horticulturae</italic></source><year>2007</year><volume>111</volume><issue>2</issue><fpage>120</fpage><lpage>127</lpage><pub-id pub-id-type="other">2-s2.0-33751501376</pub-id></element-citation></ref><ref id="B98"><label>98</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jahfar</surname><given-names>M</given-names></name><name><surname>Vijayan</surname><given-names>KK</given-names></name><name><surname>Azadi</surname><given-names>P</given-names></name></person-group><article-title>Studies on a polysaccharide from the fruit rind of <italic>Punica granatum</italic></article-title><source><italic>Research Journal of Chemistry and Environment</italic></source><year>2003</year><volume>7</volume><issue>1</issue><fpage>43</fpage><lpage>50</lpage></element-citation></ref><ref id="B99"><label>99</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>MY</given-names></name><name><surname>Seeram</surname><given-names>NP</given-names></name><name><surname>Heber</surname><given-names>D</given-names></name></person-group><article-title>Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor</article-title><source><italic>The Journal of Nutritional Biochemistry</italic></source><year>2008</year><volume>19</volume><issue>12</issue><fpage>848</fpage><lpage>855</lpage><pub-id pub-id-type="other">2-s2.0-53249094494</pub-id><pub-id pub-id-type="pmid">18479901</pub-id></element-citation></ref><ref id="B100"><label>100</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>DiSilvestro</surname><given-names>RA</given-names></name><name><surname>DiSilvestro</surname><given-names>DJ</given-names></name><name><surname>DiSilvestro</surname><given-names>DJ</given-names></name></person-group><article-title>Pomegranate extract mouth rinsing effects on saliva measures relevant to gingivitis risk</article-title><source><italic>Phytotherapy Research</italic></source><year>2009</year><volume>23</volume><issue>8</issue><fpage>1123</fpage><lpage>1127</lpage><pub-id pub-id-type="other">2-s2.0-68049097891</pub-id><pub-id pub-id-type="pmid">19170139</pub-id></element-citation></ref><ref id="B101"><label>101</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seeram</surname><given-names>NP</given-names></name><name><surname>Aviram</surname><given-names>M</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name><etal></etal></person-group><article-title>Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States</article-title><source><italic>Journal of Agricultural and Food Chemistry</italic></source><year>2008</year><volume>56</volume><issue>4</issue><fpage>1415</fpage><lpage>1422</lpage><pub-id pub-id-type="other">2-s2.0-40549091931</pub-id><pub-id pub-id-type="pmid">18220345</pub-id></element-citation></ref><ref id="B102"><label>102</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kelawala</surname><given-names>NS</given-names></name><name><surname>Ananthanarayan</surname><given-names>L</given-names></name></person-group><article-title>Antioxidant activity of selected foodstuffs</article-title><source><italic>International Journal of Food Sciences and Nutrition</italic></source><year>2004</year><volume>55</volume><issue>6</issue><fpage>511</fpage><lpage>516</lpage><pub-id pub-id-type="other">2-s2.0-11344251054</pub-id><pub-id pub-id-type="pmid">15762315</pub-id></element-citation></ref><ref id="B103"><label>103</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schäfer</surname><given-names>A</given-names></name><name><surname>Chovanová</surname><given-names>Z</given-names></name><name><surname>Muchová</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol)</article-title><source><italic>Biomedicine and Pharmacotherapy</italic></source><year>2006</year><volume>60</volume><issue>1</issue><fpage>5</fpage><lpage>9</lpage><pub-id pub-id-type="other">2-s2.0-29244453202</pub-id><pub-id pub-id-type="pmid">16330178</pub-id></element-citation></ref><ref id="B104"><label>104</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Seeram</surname><given-names>NP</given-names></name><name><surname>Adams</surname><given-names>LS</given-names></name><name><surname>Henning</surname><given-names>SM</given-names></name><etal></etal></person-group><article-title><italic>In vitro</italic> antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice</article-title><source><italic>The Journal of Nutritional Biochemistry</italic></source><year>2005</year><volume>16</volume><issue>6</issue><fpage>360</fpage><lpage>367</lpage><pub-id pub-id-type="other">2-s2.0-20144381777</pub-id><pub-id pub-id-type="pmid">15936648</pub-id></element-citation></ref><ref id="B105"><label>105</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Meenakshi</surname><given-names>S</given-names></name><name><surname>Kalpana</surname><given-names>G</given-names></name><name><surname>Khursheed</surname><given-names>AK</given-names></name><name><surname>Tariq</surname><given-names>MH</given-names></name></person-group><article-title>Bioavailable constituents/metabolites of pomegranate (<italic>Punica granatum</italic> L) preferentially inhibit COX2 activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes <italic>in vitro</italic></article-title><source><italic>Journal of Inflammation</italic></source><year>2008</year><volume>13</volume><issue>5</issue><fpage>p. 9</fpage></element-citation></ref></ref-list></back><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Therapeutically beneficial uses of<italic> Punica</italic> fruit. Pomegranate fruit has been proven to act against various diseases like cancer, cardiovascular disorders, diabetes, AIDS, and Alzheimer's disease.</p></caption><graphic xlink:href="BMRI2014-686921.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Effect of PME on MMP-9 transcription in MCF7 cells. (a) MCF7 cells were incubated with PME (40, 80, and 160 <italic>μ</italic>g/mL) and E2 (10 nM) for 24 hrs and semiquantitative RT-PCR was done. (b) shows the ratio of density of MMP-9 gene expression to that of endogenous control GAPDH and it represents mean ± SE of 3 replicates (*<italic>P</italic> < 0.05).</p></caption><graphic xlink:href="BMRI2014-686921.002"></graphic></fig><fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Effect of PME pretreatment on E2 induced expression of c-Myc. (a) MCF7 cells were pretreated with 100 nM E2 for 4 hrs, with or without PME pretreatment (80 <italic>μ</italic>g/mL) for 12 hrs and RT-PCR was done. (b) shows the ratio of density of c-Myc gene expression to that of endogenous control GAPDH and it represents mean ± SE of 3 replicates (*<italic>P</italic> < 0.05).</p></caption><graphic xlink:href="BMRI2014-686921.003"></graphic></fig><fig id="fig4" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Effect of PME on pS2 protein expression in MCF7 cells. (a) Immunoblot result of MCF7 cells treated with 10 nM E2, PME (80 <italic>μ</italic>g/mL), 10 nM PPT, 10 nM DPN, and PME (80 <italic>μ</italic>g/mL) with 10 nM PPT or 10 nM DPN for 48 hrs. (b) Data are presented as densitometric ratio relative to nontreated control (CON) cells. The values are mean ± SE of 3 separate experiments (*<italic>P</italic> < 0.05).</p></caption><graphic xlink:href="BMRI2014-686921.004"></graphic></fig><fig id="fig5" orientation="portrait" position="float"><label>Figure 5</label><caption><p>PME increased ALP activity in MC3T3-E1 osteoblast without affecting cell proliferation. (a) Dose-dependent effect of PME on cell proliferation. MC3T3-E1 osteoblasts were treated with 0 (control), 20, 40, 80, 160, and 320 <italic>μ</italic>g/mL of PME for 48 hrs and the cell proliferation was determined by MTT assay. The cell proliferation was expressed as percentage cell viability over the untreated control. (b) Cells were treated with E2 (10 nM), PME (40, 80, and 160 <italic>μ</italic>g/mL), ICI (1 <italic>μ</italic>M) with or without PME (80 <italic>μ</italic>g/mL) for 48 hrs. ALP activity was then measured and results are expressed as percentage over the untreated control. Results are expressed as mean values ± SE of five replicates. *<italic>P</italic> < 0.05 when compared to untreated control.</p></caption><graphic xlink:href="BMRI2014-686921.005"></graphic></fig><fig id="fig6" orientation="portrait" position="float"><label>Figure 6</label><caption><p>PME did not alter lactoferrin expression in murine uterus. (a) RT-PCR detection of Lactoferrin m-RNA in sham control (SS CON) and ovariectomized mice exposed to 0.1% ethanol (vehicle control, Ovx CON), E2 (1 mg/kg bwt), PME (50, 100 mg/kg bwt), and tamoxifen (TAM, 10 mg/kg bwt) for 7 days. (b) shows the ratio of density of target gene expression to that of endogenous control beta-actin and it represents mean ± SE of three replicates.</p></caption><graphic xlink:href="BMRI2014-686921.006"></graphic></fig><fig id="fig7" orientation="portrait" position="float"><label>Figure 7</label><caption><p>Biological effects of PME. PME was found to be antiestrogenic in breast, exhibited cardioprotective and osteoprotective effects, and had no estrogenicity in uterus. It did not induce DNA adduct formation or oxidative DNA damage and suppressed TNF <italic>α</italic>-mediated endothelial cell apoptosis.</p></caption><graphic xlink:href="BMRI2014-686921.007"></graphic></fig><table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label><caption><p>Principal constituents of different parts of pomegranate tree and fruit. The different parts of pomegranate plant like peel, root, bark, flower, leaves, and so forth exhibit different phytochemicals.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Pomegranate peel</th><th align="left" rowspan="1" colspan="1">Pomegranate juice</th><th align="left" rowspan="1" colspan="1">Pomegranate root <break></break>and bark</th><th align="left" rowspan="1" colspan="1">Pomegranate flower</th><th align="left" rowspan="1" colspan="1">Pomegranate leaves</th><th align="left" rowspan="1" colspan="1">Pomegranate seed</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">(i) Gallic acid<break></break>(ii) Ellagic acid<break></break>(iii) Punicalin<break></break>(iv) Punicalagin<break></break>(v) Caffeic acid<break></break>(vi) Ellagitannins<break></break>(vii) Pelletierine alkaloids<break></break>(viii) Luteolin<break></break>(ix) Kaempferol<break></break>(x) Quercetin<break></break></td><td align="left" rowspan="1" colspan="1">(i) Simple sugars<break></break>(ii) Aliphatic organic acids<break></break>(iii) Gallic acid<break></break>(iv) Ellagic acid<break></break>(v) Quinic acid<break></break>(vi) Flavonols<break></break>(vii) Amino acids<break></break>(viii) Minerals<break></break>(ix) EGCG<break></break>(x) Ascorbic acid</td><td align="left" rowspan="1" colspan="1">(i) Ellagitannins<break></break>(ii) Piperidine alkaloids<break></break>(iii) Pyrrolidine alkaloid<break></break>(iv) Pelletierine alkaloids</td><td align="left" rowspan="1" colspan="1">(i) Gallic acids<break></break>(ii) Ursolic acid<break></break>(iii) Triterpenoids<break></break>(iv) Fatty acids</td><td align="left" rowspan="1" colspan="1">(i) Carbohydrates<break></break>(ii) Reducing sugars<break></break>(iii) Sterols<break></break>(iv) Saponins<break></break>(v) Flavanoids<break></break>(vi) Tannins<break></break>(vii) Piperidine alkaloids<break></break>(viii) Flavone<break></break>(ix) Glycoside<break></break>(x) Ellagitannins</td><td align="left" rowspan="1" colspan="1">(i) 3,3′-Di-<italic>O</italic>-methylellagic acid<break></break>(ii) 3,3′,4′-Tri-<italic>O</italic>-methylellagic acid<break></break>(iii) Punicic acid<break></break>(iv) Oleic acid<break></break>(v) Palmitic acid<break></break>(vi) Stearic acid<break></break>(vii) Linoleic acid<break></break>(viii) Sterols<break></break>(ix) Tocopherols<break></break>(x) Sex steroids</td></tr><tr><td align="left" colspan="6" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="1" colspan="1">References [<xref rid="B20" ref-type="bibr">20</xref>–<xref rid="B26" ref-type="bibr">26</xref>]</td><td align="left" rowspan="1" colspan="1">References [<xref rid="B15" ref-type="bibr">15</xref>, <xref rid="B20" ref-type="bibr">20</xref>, <xref rid="B26" ref-type="bibr">26</xref>–<xref rid="B30" ref-type="bibr">30</xref>]</td><td align="left" rowspan="1" colspan="1">References [<xref rid="B21" ref-type="bibr">21</xref>, <xref rid="B23" ref-type="bibr">23</xref>]</td><td align="left" rowspan="1" colspan="1">References [<xref rid="B31" ref-type="bibr">31</xref>–<xref rid="B33" ref-type="bibr">33</xref>]</td><td align="left" rowspan="1" colspan="1">References [<xref rid="B21" ref-type="bibr">21</xref>, <xref rid="B22" ref-type="bibr">22</xref>, <xref rid="B34" ref-type="bibr">34</xref>, <xref rid="B35" ref-type="bibr">35</xref>]</td><td align="left" rowspan="1" colspan="1">References [<xref rid="B36" ref-type="bibr">36</xref>–<xref rid="B41" ref-type="bibr">41</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label><caption><p>Effect of E2, PME, and tamoxifen on chosen markers of bone metabolism of ovariectomized mice. Serum calcium, phosphorus, and Alkaline Phosphatase (ALP) levels of sham control (SS Con) and Ovx mice exposed to 0.1% ethanol (vehicle control), E2 (1 mg/kg bwt), PME (50, 100 mg/kg bwt), and tamoxifen (TAM, 10 mg/kg bwt) for 7 days (bwt = body weight). Data are expressed as mean ± SE (<italic>n</italic> = 5).</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"> </th><th align="center" rowspan="1" colspan="1">Sham control</th><th align="center" rowspan="1" colspan="1">OVX control</th><th align="center" rowspan="1" colspan="1">E2 <break></break>(1 mg/kg bwt)</th><th align="center" rowspan="1" colspan="1">PME <break></break>(50 mg/kg bwt)</th><th align="center" rowspan="1" colspan="1">PME <break></break>(100 mg/kg bwt)</th><th align="center" rowspan="1" colspan="1">TAM <break></break>(10 mg/kg bwt)</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1">Calcium (mg/dL)</td><td align="center" rowspan="1" colspan="1">9.46 ± 0.313</td><td align="center" rowspan="1" colspan="1">10.94 ± 1.18 </td><td align="center" rowspan="1" colspan="1">8.188 ± 0.7040<sup>a </sup></td><td align="center" rowspan="1" colspan="1">8.5 ± 0.707 </td><td align="center" rowspan="1" colspan="1">9.09 ± 0.194 </td><td align="center" rowspan="1" colspan="1">9.908 ± 0.165</td></tr><tr><td align="left" rowspan="1" colspan="1">Phosphorus (mg/dL)</td><td align="center" rowspan="1" colspan="1">7.43 ± 0.63</td><td align="center" rowspan="1" colspan="1">8.818 ± 0.698 </td><td align="center" rowspan="1" colspan="1">8.026 ± 1.066 </td><td align="center" rowspan="1" colspan="1">7.516 ± 1.731 </td><td align="center" rowspan="1" colspan="1">8.78 ± 1.980</td><td align="center" rowspan="1" colspan="1">8.146 ± 0.0680</td></tr><tr><td align="left" rowspan="1" colspan="1">ALP (U/L)</td><td align="center" rowspan="1" colspan="1">140.6 ± 11.28 </td><td align="center" rowspan="1" colspan="1">181.8 ± 34.07<sup>a </sup></td><td align="center" rowspan="1" colspan="1">115.2 ± 23.61<sup>b </sup></td><td align="center" rowspan="1" colspan="1">130.4 ± 12.77</td><td align="center" rowspan="1" colspan="1">120 ± 9.02<sup>b </sup></td><td align="center" rowspan="1" colspan="1">134.6 ± 17.54<sup>b </sup></td></tr></tbody></table><table-wrap-foot><fn><p><sup>a</sup><italic>P</italic> < 0.05 versus sham control, <sup>b</sup><italic>P</italic> < 0.05 versus ovx control.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Bois/explor/OrangerV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001351 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001351 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Bois
|area= OrangerV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé=
|texte=
}}
| This area was generated with Dilib version V0.6.25. |  |