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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications</title><author><name sortKey="Uchide, Noboru" sort="Uchide, Noboru" uniqKey="Uchide N" first="Noboru" last="Uchide">Noboru Uchide</name></author><author><name sortKey="Toyoda, Hiroo" sort="Toyoda, Hiroo" uniqKey="Toyoda H" first="Hiroo" last="Toyoda">Hiroo Toyoda</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21358592</idno><idno type="pmc">6259602</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259602</idno><idno type="RBID">PMC:6259602</idno><idno type="doi">10.3390/molecules23100000</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">000F56</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F56</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications</title><author><name sortKey="Uchide, Noboru" sort="Uchide, Noboru" uniqKey="Uchide N" first="Noboru" last="Uchide">Noboru Uchide</name></author><author><name sortKey="Toyoda, Hiroo" sort="Toyoda, Hiroo" uniqKey="Toyoda H" first="Hiroo" last="Toyoda">Hiroo Toyoda</name></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>With the appearance of the novel influenza A (H1N1) virus 2009 strain we have experienced a new influenza pandemic and many patients have died from severe complications associated with this pandemic despite receiving intensive care. This suggests that a definitive medical treatment for severe influenza-associated complications has not yet been established. Many studies have shown that superoxide anion produced by macrophages infiltrated into the virus-infected organs is implicated in the development of severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocabamate, <italic>N</italic>-acetyl-<sc>l</sc>-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin, resveratrol, (+)-vitisin A, ambroxol, ascorbic acid, 5,7,4-trihydroxy-8-methoxyflavone, catechins, quercetin 3-rhamnoside, iso- quercetin and oligonol, inhibit the proliferation of influenza virus and scavenge superoxide anion. The combination of antioxidants with antiviral drugs synergistically reduces the lethal effects of influenza virus infections. These results suggest that an agent with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with severe influenza-associated complications. This review article updates knowledge of antioxidant therapy as a potential approach to severe influenza-associated complications.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Peiris, J S" uniqKey="Peiris J">J.S. Peiris</name></author><author><name sortKey="Tu, W W" uniqKey="Tu W">W.W. Tu</name></author><author><name sortKey="Yen, H L" uniqKey="Yen H">H.L. Yen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chang, L Y" uniqKey="Chang L">L.Y. Chang</name></author><author><name sortKey="Shih, S R" uniqKey="Shih S">S.R. Shih</name></author><author><name sortKey="Shao, P L" uniqKey="Shao P">P.L. Shao</name></author><author><name sortKey="Huang, D T" uniqKey="Huang D">D.T. Huang</name></author><author><name sortKey="Huang, L M" uniqKey="Huang L">L.M. Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rothberg, M B" uniqKey="Rothberg M">M.B. Rothberg</name></author><author><name sortKey="Haessler, S D" uniqKey="Haessler S">S.D. Haessler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Girard, M P" uniqKey="Girard M">M.P. Girard</name></author><author><name sortKey="Tam, J S" uniqKey="Tam J">J.S. Tam</name></author><author><name sortKey="Assossou, O M" uniqKey="Assossou O">O.M. Assossou</name></author><author><name sortKey="Kieny, M P" uniqKey="Kieny M">M.P. Kieny</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kamps, B S" uniqKey="Kamps B">B.S. Kamps</name></author><author><name sortKey="Reyes Teran, G" uniqKey="Reyes Teran G">G. Reyes-Terán</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beigel, J" uniqKey="Beigel J">J. Beigel</name></author><author><name sortKey="Bray, M" uniqKey="Bray M">M. Bray</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sugaya, N" uniqKey="Sugaya N">N. Sugaya</name></author><author><name sortKey="Ohashi, Y" uniqKey="Ohashi Y">Y. Ohashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bearman, G M" uniqKey="Bearman G">G.M. Bearman</name></author><author><name sortKey="Shankaran, S" uniqKey="Shankaran S">S. Shankaran</name></author><author><name sortKey="Elam, K" uniqKey="Elam K">K. Elam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nasu, T" uniqKey="Nasu T">T. Nasu</name></author><author><name sortKey="Ogawa, D" uniqKey="Ogawa D">D. Ogawa</name></author><author><name sortKey="Wada, J" uniqKey="Wada J">J. Wada</name></author><author><name sortKey="Makino, H" uniqKey="Makino H">H. Makino</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Renaud, C" uniqKey="Renaud C">C. Renaud</name></author><author><name sortKey="Pergam, S A" uniqKey="Pergam S">S.A. Pergam</name></author><author><name sortKey="Polyak, C" uniqKey="Polyak C">C. Polyak</name></author><author><name sortKey="Jain, R" uniqKey="Jain R">R. Jain</name></author><author><name sortKey="Kuypers, J" uniqKey="Kuypers J">J. Kuypers</name></author><author><name sortKey="Englund, J A" uniqKey="Englund J">J.A. Englund</name></author><author><name sortKey="Corey, L" uniqKey="Corey L">L. Corey</name></author><author><name sortKey="Boeckh, M J" uniqKey="Boeckh M">M.J. Boeckh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cunha, B A" uniqKey="Cunha B">B.A. Cunha</name></author><author><name sortKey="Syed, U" uniqKey="Syed U">U. Syed</name></author><author><name sortKey="Mickail, N" uniqKey="Mickail N">N. Mickail</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, J T" uniqKey="Nguyen J">J.T. Nguyen</name></author><author><name sortKey="Hoopes, J D" uniqKey="Hoopes J">J.D. Hoopes</name></author><author><name sortKey="Le, M H" uniqKey="Le M">M.H. Le</name></author><author><name sortKey="Smee, D F" uniqKey="Smee D">D.F. Smee</name></author><author><name sortKey="Patick, A K" uniqKey="Patick A">A.K. Patick</name></author><author><name sortKey="Faix, D J" uniqKey="Faix D">D.J. Faix</name></author><author><name sortKey="Blair, P J" uniqKey="Blair P">P.J. Blair</name></author><author><name sortKey="De Jong, M D" uniqKey="De Jong M">M.D. de Jong</name></author><author><name sortKey="Prichard, M N" uniqKey="Prichard M">M.N. Prichard</name></author><author><name sortKey="Went, G T" uniqKey="Went G">G.T. Went</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tumpey, T M" uniqKey="Tumpey T">T.M. Tumpey</name></author><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A. García-Sastre</name></author><author><name sortKey="Taubenberger, J K" uniqKey="Taubenberger J">J.K. Taubenberger</name></author><author><name sortKey="Palese, P" uniqKey="Palese P">P. Palese</name></author><author><name sortKey="Swayne, D E" uniqKey="Swayne D">D.E. Swayne</name></author><author><name sortKey="Pantin Jackwood, M J" uniqKey="Pantin Jackwood M">M.J. Pantin-Jackwood</name></author><author><name sortKey="Schultz Cherry, S" uniqKey="Schultz Cherry S">S. Schultz-Cherry</name></author><author><name sortKey="Sol Rzano, A" uniqKey="Sol Rzano A">A. Solórzano</name></author><author><name sortKey="Van Rooijen, N" uniqKey="Van Rooijen N">N. Van Rooijen</name></author><author><name sortKey="Katz, J M" uniqKey="Katz J">J.M. Katz</name></author><author><name sortKey="Basler, C F" uniqKey="Basler C">C.F. Basler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H. Toyoda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akaike, T" uniqKey="Akaike T">T. Akaike</name></author><author><name sortKey="Suga, M" uniqKey="Suga M">M. Suga</name></author><author><name sortKey="Maeda, H" uniqKey="Maeda H">H. Maeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H. Toyoda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H. Toyoda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oda, T" uniqKey="Oda T">T. Oda</name></author><author><name sortKey="Akaike, T" uniqKey="Akaike T">T. Akaike</name></author><author><name sortKey="Hamamoto, T" uniqKey="Hamamoto T">T. Hamamoto</name></author><author><name sortKey="Suzuki, F" uniqKey="Suzuki F">F. Suzuki</name></author><author><name sortKey="Hirano, T" uniqKey="Hirano T">T. Hirano</name></author><author><name sortKey="Maeda, H" uniqKey="Maeda H">H. Maeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sidwell, R W" uniqKey="Sidwell R">R.W. Sidwell</name></author><author><name sortKey="Huffman, J H" uniqKey="Huffman J">J.H. Huffman</name></author><author><name sortKey="Bailey, K W" uniqKey="Bailey K">K.W. Bailey</name></author><author><name sortKey="Wong, M H" uniqKey="Wong M">M.H. Wong</name></author><author><name sortKey="Nimrod, A" uniqKey="Nimrod A">A. Nimrod</name></author><author><name sortKey="Panet, A" uniqKey="Panet A">A. Panet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Serkedjieva, J" uniqKey="Serkedjieva J">J. Serkedjieva</name></author><author><name sortKey="Roeva, I" uniqKey="Roeva I">I. Roeva</name></author><author><name sortKey="Angelova, M" uniqKey="Angelova M">M. Angelova</name></author><author><name sortKey="Dolashka, P" uniqKey="Dolashka P">P. Dolashka</name></author><author><name sortKey="Voelter, W G" uniqKey="Voelter W">W.G. Voelter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akaike, T" uniqKey="Akaike T">T. Akaike</name></author><author><name sortKey="Ando, M" uniqKey="Ando M">M. Ando</name></author><author><name sortKey="Oda, T" uniqKey="Oda T">T. Oda</name></author><author><name sortKey="Doi, T" uniqKey="Doi T">T. Doi</name></author><author><name sortKey="Ijiri, S" uniqKey="Ijiri S">S. Ijiri</name></author><author><name sortKey="Araki, S" uniqKey="Araki S">S. Araki</name></author><author><name sortKey="Maeda, H" uniqKey="Maeda H">H. Maeda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suliman, H B" uniqKey="Suliman H">H.B. Suliman</name></author><author><name sortKey="Ryan, L K" uniqKey="Ryan L">L.K. Ryan</name></author><author><name sortKey="Bishop, L" uniqKey="Bishop L">L. Bishop</name></author><author><name sortKey="Folz, R J" uniqKey="Folz R">R.J. Folz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Snelgrove, R J" uniqKey="Snelgrove R">R.J. Snelgrove</name></author><author><name sortKey="Edwards, L" uniqKey="Edwards L">L. Edwards</name></author><author><name sortKey="Rae, A J" uniqKey="Rae A">A.J. Rae</name></author><author><name sortKey="Hussell, T" uniqKey="Hussell T">T. Hussell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shi, Y" uniqKey="Shi Y">Y. Shi</name></author><author><name sortKey="Niculescu, R" uniqKey="Niculescu R">R. Niculescu</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D. Wang</name></author><author><name sortKey="Patel, S" uniqKey="Patel S">S. Patel</name></author><author><name sortKey="Davenpeck, K L" uniqKey="Davenpeck K">K.L. Davenpeck</name></author><author><name sortKey="Zalewski, A" uniqKey="Zalewski A">A. Zalewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Ohyama, K" uniqKey="Ohyama K">K. Ohyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Ohyama, K" uniqKey="Ohyama K">K. Ohyama</name></author><author><name sortKey="Bessho, T" uniqKey="Bessho T">T. Bessho</name></author><author><name sortKey="Yuan, B" uniqKey="Yuan B">B. Yuan</name></author><author><name sortKey="Yamakawa, T" uniqKey="Yamakawa T">T. Yamakawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knobil, K" uniqKey="Knobil K">K. Knobil</name></author><author><name sortKey="Choi, A M" uniqKey="Choi A">A.M. Choi</name></author><author><name sortKey="Weigand, G W" uniqKey="Weigand G">G.W. Weigand</name></author><author><name sortKey="Jacoby, D B" uniqKey="Jacoby D">D.B. Jacoby</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lowy, R J" uniqKey="Lowy R">R.J. Lowy</name></author><author><name sortKey="Dimitrov, D S" uniqKey="Dimitrov D">D.S. Dimitrov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mckinney, L C" uniqKey="Mckinney L">L.C. McKinney</name></author><author><name sortKey="Galliger, S J" uniqKey="Galliger S">S.J. Galliger</name></author><author><name sortKey="Lowy, R J" uniqKey="Lowy R">R.J. Lowy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, K" uniqKey="Chen K">K. Chen</name></author><author><name sortKey="Long, Y M" uniqKey="Long Y">Y.M. Long</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H. Wang</name></author><author><name sortKey="Lan, L" uniqKey="Lan L">L. Lan</name></author><author><name sortKey="Lin, Z H" uniqKey="Lin Z">Z.H. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cuzzocrea, S" uniqKey="Cuzzocrea S">S. Cuzzocrea</name></author><author><name sortKey="Chatterjee, P K" uniqKey="Chatterjee P">P.K. Chatterjee</name></author><author><name sortKey="Mazzon, E" uniqKey="Mazzon E">E. Mazzon</name></author><author><name sortKey="Dugo, L" uniqKey="Dugo L">L. Dugo</name></author><author><name sortKey="Serraino, I" uniqKey="Serraino I">I. Serraino</name></author><author><name sortKey="Britti, D" uniqKey="Britti D">D. Britti</name></author><author><name sortKey="Mazzullo, G" uniqKey="Mazzullo G">G. Mazzullo</name></author><author><name sortKey="Caputi, A P" uniqKey="Caputi A">A.P. Caputi</name></author><author><name sortKey="Thiemermann, C" uniqKey="Thiemermann C">C. Thiemermann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mallick, I H" uniqKey="Mallick I">I.H. Mallick</name></author><author><name sortKey="Yang, W X" uniqKey="Yang W">W.X. Yang</name></author><author><name sortKey="Winslet, M C" uniqKey="Winslet M">M.C. Winslet</name></author><author><name sortKey="Seifalian, A M" uniqKey="Seifalian A">A.M. Seifalian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, C H" uniqKey="Yang C">C.H. Yang</name></author><author><name sortKey="Fang, I M" uniqKey="Fang I">I.M. Fang</name></author><author><name sortKey="Lin, C P" uniqKey="Lin C">C.P. Lin</name></author><author><name sortKey="Yang, C M" uniqKey="Yang C">C.M. Yang</name></author><author><name sortKey="Chen, M S" uniqKey="Chen M">M.S. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, C H" uniqKey="Kim C">C.H. Kim</name></author><author><name sortKey="Kim, J H" uniqKey="Kim J">J.H. Kim</name></author><author><name sortKey="Hsu, C Y" uniqKey="Hsu C">C.Y. Hsu</name></author><author><name sortKey="Ahn, Y S" uniqKey="Ahn Y">Y.S. Ahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oxford, J S" uniqKey="Oxford J">J.S. Oxford</name></author><author><name sortKey="Perrin, D D" uniqKey="Perrin D">D.D. Perrin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Si, X" uniqKey="Si X">X. Si</name></author><author><name sortKey="Mcmanus, B M" uniqKey="Mcmanus B">B.M. McManus</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J. Zhang</name></author><author><name sortKey="Yuan, J" uniqKey="Yuan J">J. Yuan</name></author><author><name sortKey="Cheung, C" uniqKey="Cheung C">C. Cheung</name></author><author><name sortKey="Esfandiarei, M" uniqKey="Esfandiarei M">M. Esfandiarei</name></author><author><name sortKey="Suarez, A" uniqKey="Suarez A">A. Suarez</name></author><author><name sortKey="Morgan, A" uniqKey="Morgan A">A. Morgan</name></author><author><name sortKey="Luo, H" uniqKey="Luo H">H. Luo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Krenn, B M" uniqKey="Krenn B">B.M. Krenn</name></author><author><name sortKey="Holzer, B" uniqKey="Holzer B">B. Holzer</name></author><author><name sortKey="Gaudernak, E" uniqKey="Gaudernak E">E. Gaudernak</name></author><author><name sortKey="Triendl, A" uniqKey="Triendl A">A. Triendl</name></author><author><name sortKey="Van Kuppeveld, F J" uniqKey="Van Kuppeveld F">F.J. van Kuppeveld</name></author><author><name sortKey="Seipelt, J" uniqKey="Seipelt J">J. Seipelt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Ohyama, K" uniqKey="Ohyama K">K. Ohyama</name></author><author><name sortKey="Bessho, T" uniqKey="Bessho T">T. Bessho</name></author><author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H. Toyoda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiou, W F" uniqKey="Chiou W">W.F. Chiou</name></author><author><name sortKey="Chen, C C" uniqKey="Chen C">C.C. Chen</name></author><author><name sortKey="Wei, B L" uniqKey="Wei B">B.L. Wei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kelly, G S" uniqKey="Kelly G">G.S. Kelly</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saito, T" uniqKey="Saito T">T. Saito</name></author><author><name sortKey="Tanaka, M" uniqKey="Tanaka M">M. Tanaka</name></author><author><name sortKey="Yamaguchi, I" uniqKey="Yamaguchi I">I. Yamaguchi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, C" uniqKey="Lin C">C. Lin</name></author><author><name sortKey="Zimmer, S G" uniqKey="Zimmer S">S.G. Zimmer</name></author><author><name sortKey="Lu, Z" uniqKey="Lu Z">Z. Lu</name></author><author><name sortKey="Holland, R E" uniqKey="Holland R">R.E. Holland</name></author><author><name sortKey="Dong, Q" uniqKey="Dong Q">Q. Dong</name></author><author><name sortKey="Chambers, T M" uniqKey="Chambers T">T.M. Chambers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geiler, J" uniqKey="Geiler J">J. Geiler</name></author><author><name sortKey="Michaelis, M" uniqKey="Michaelis M">M. Michaelis</name></author><author><name sortKey="Naczk, P" uniqKey="Naczk P">P. Naczk</name></author><author><name sortKey="Leutz, A" uniqKey="Leutz A">A. Leutz</name></author><author><name sortKey="Langer, K" uniqKey="Langer K">K. Langer</name></author><author><name sortKey="Doerr, H W" uniqKey="Doerr H">H.W. Doerr</name></author><author><name sortKey="Cinatl, J" uniqKey="Cinatl J">J. Cinatl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ungheri, D" uniqKey="Ungheri D">D. Ungheri</name></author><author><name sortKey="Pisani, C" uniqKey="Pisani C">C. Pisani</name></author><author><name sortKey="Sanson, G" uniqKey="Sanson G">G. Sanson</name></author><author><name sortKey="Bertani, A" uniqKey="Bertani A">A. Bertani</name></author><author><name sortKey="Schioppacassi, G" uniqKey="Schioppacassi G">G. Schioppacassi</name></author><author><name sortKey="Delgado, R" uniqKey="Delgado R">R. Delgado</name></author><author><name sortKey="Sironi, M" uniqKey="Sironi M">M. Sironi</name></author><author><name sortKey="Ghezzi, P" uniqKey="Ghezzi P">P. Ghezzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghezzi, P" uniqKey="Ghezzi P">P. Ghezzi</name></author><author><name sortKey="Ungheri, D" uniqKey="Ungheri D">D. Ungheri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garozzo, A" uniqKey="Garozzo A">A. Garozzo</name></author><author><name sortKey="Tempera, G" uniqKey="Tempera G">G. Tempera</name></author><author><name sortKey="Ungheri, D" uniqKey="Ungheri D">D. Ungheri</name></author><author><name sortKey="Timpanaro, R" uniqKey="Timpanaro R">R. Timpanaro</name></author><author><name sortKey="Castro, A" uniqKey="Castro A">A. Castro</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Flora, S" uniqKey="De Flora S">S. De Flora</name></author><author><name sortKey="Grassi, C" uniqKey="Grassi C">C. Grassi</name></author><author><name sortKey="Carati, L" uniqKey="Carati L">L. Carati</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lai, K Y" uniqKey="Lai K">K.Y. Lai</name></author><author><name sortKey="Ng, W Y" uniqKey="Ng W">W.Y. Ng</name></author><author><name sortKey="Osburga Chan, P K" uniqKey="Osburga Chan P">P.K. Osburga Chan</name></author><author><name sortKey="Wong, K F" uniqKey="Wong K">K.F. Wong</name></author><author><name sortKey="Cheng, F" uniqKey="Cheng F">F. Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cai, J" uniqKey="Cai J">J. Cai</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Seth, S" uniqKey="Seth S">S. Seth</name></author><author><name sortKey="Furukawa, S" uniqKey="Furukawa S">S. Furukawa</name></author><author><name sortKey="Compans, R W" uniqKey="Compans R">R.W. Compans</name></author><author><name sortKey="Jones, D P" uniqKey="Jones D">D.P. Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nencioni, L" uniqKey="Nencioni L">L. Nencioni</name></author><author><name sortKey="Iuvara, A" uniqKey="Iuvara A">A. Iuvara</name></author><author><name sortKey="Aquilano, K" uniqKey="Aquilano K">K. Aquilano</name></author><author><name sortKey="Ciriolo, M R" uniqKey="Ciriolo M">M.R. Ciriolo</name></author><author><name sortKey="Cozzolino, F" uniqKey="Cozzolino F">F. Cozzolino</name></author><author><name sortKey="Rotilio, G" uniqKey="Rotilio G">G. Rotilio</name></author><author><name sortKey="Garaci, E" uniqKey="Garaci E">E. Garaci</name></author><author><name sortKey="Palamara, A T" uniqKey="Palamara A">A.T. Palamara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Floriano Sanchez, E" uniqKey="Floriano Sanchez E">E. Floriano-Sanchez</name></author><author><name sortKey="Villanueva, C" uniqKey="Villanueva C">C. Villanueva</name></author><author><name sortKey="Medina Campos, O N" uniqKey="Medina Campos O">O.N. Medina-Campos</name></author><author><name sortKey="Rocha, D" uniqKey="Rocha D">D. Rocha</name></author><author><name sortKey="Sanchez Gonzalez, D J" uniqKey="Sanchez Gonzalez D">D.J. Sanchez-Gonzalez</name></author><author><name sortKey="Cardenas Rodriguez, N" uniqKey="Cardenas Rodriguez N">N. Cardenas-Rodriguez</name></author><author><name sortKey="Pedraza Chaverri, J" uniqKey="Pedraza Chaverri J">J. Pedraza-Chaverri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, J M" uniqKey="Lu J">J.M. Lü</name></author><author><name sortKey="Nurko, J" uniqKey="Nurko J">J. Nurko</name></author><author><name sortKey="Weakley, S M" uniqKey="Weakley S">S.M. Weakley</name></author><author><name sortKey="Jiang, J" uniqKey="Jiang J">J. Jiang</name></author><author><name sortKey="Kougias, P" uniqKey="Kougias P">P. Kougias</name></author><author><name sortKey="Lin, P H" uniqKey="Lin P">P.H. Lin</name></author><author><name sortKey="Yao, Q" uniqKey="Yao Q">Q. Yao</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Uchide, N" uniqKey="Uchide N">N. Uchide</name></author><author><name sortKey="Ohyama, K" uniqKey="Ohyama K">K. Ohyama</name></author><author><name sortKey="Bessho, T" uniqKey="Bessho T">T. Bessho</name></author><author><name sortKey="Toyoda, H" uniqKey="Toyoda H">H. Toyoda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, Q" uniqKey="Chen Q">Q. Chen</name></author><author><name sortKey="Andrea, B J" uniqKey="Andrea B">B.J. Andrea</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Eads, D" uniqKey="Eads D">D. Eads</name></author><author><name sortKey="Hansen, R" uniqKey="Hansen R">R. Hansen</name></author><author><name sortKey="Oyegunwa, A" uniqKey="Oyegunwa A">A. Oyegunwa</name></author><author><name sortKey="Cecil, C" uniqKey="Cecil C">C. Cecil</name></author><author><name sortKey="Culver, C" uniqKey="Culver C">C. Culver</name></author><author><name sortKey="Scholle, F" uniqKey="Scholle F">F. Scholle</name></author><author><name sortKey="Petty, I" uniqKey="Petty I">I. Petty</name></author><author><name sortKey="Laster, S" uniqKey="Laster S">S. Laster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Craigo, J" uniqKey="Craigo J">J. Craigo</name></author><author><name sortKey="Callahan, M" uniqKey="Callahan M">M. Callahan</name></author><author><name sortKey="Huang, R C" uniqKey="Huang R">R.C. Huang</name></author><author><name sortKey="Delucia, A L" uniqKey="Delucia A">A.L. DeLucia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tagaya, M" uniqKey="Tagaya M">M. Tagaya</name></author><author><name sortKey="Henomatsu, N" uniqKey="Henomatsu N">N. Henomatsu</name></author><author><name sortKey="Yoshimori, T" uniqKey="Yoshimori T">T. Yoshimori</name></author><author><name sortKey="Yamamoto, A" uniqKey="Yamamoto A">A. Yamamoto</name></author><author><name sortKey="Tashiro, Y" uniqKey="Tashiro Y">Y. Tashiro</name></author><author><name sortKey="Mizushima, S" uniqKey="Mizushima S">S. Mizushima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nozoe, T" uniqKey="Nozoe T">T. Nozoe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miyamoto, D" uniqKey="Miyamoto D">D. Miyamoto</name></author><author><name sortKey="Kusagaya, Y" uniqKey="Kusagaya Y">Y. Kusagaya</name></author><author><name sortKey="Endo, N" uniqKey="Endo N">N. Endo</name></author><author><name sortKey="Sometani, A" uniqKey="Sometani A">A. Sometani</name></author><author><name sortKey="Takeo, S" uniqKey="Takeo S">S. Takeo</name></author><author><name sortKey="Suzuki, T" uniqKey="Suzuki T">T. Suzuki</name></author><author><name sortKey="Arima, Y" uniqKey="Arima Y">Y. Arima</name></author><author><name sortKey="Nakajima, K" uniqKey="Nakajima K">K. Nakajima</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arima, Y" uniqKey="Arima Y">Y. Arima</name></author><author><name sortKey="Hatanaka, A" uniqKey="Hatanaka A">A. Hatanaka</name></author><author><name sortKey="Tsukihara, S" uniqKey="Tsukihara S">S. Tsukihara</name></author><author><name sortKey="Fujimoto, K" uniqKey="Fujimoto K">K. Fujimoto</name></author><author><name sortKey="Fukuda, K" uniqKey="Fukuda K">K. Fukuda</name></author><author><name sortKey="Sakurai, H" uniqKey="Sakurai H">H. Sakurai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martinez, J" uniqKey="Martinez J">J. Martinez</name></author><author><name sortKey="Moreno, J J" uniqKey="Moreno J">J.J. Moreno</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Palamara, A T" uniqKey="Palamara A">A.T. Palamara</name></author><author><name sortKey="Nencioni, L" uniqKey="Nencioni L">L. Nencioni</name></author><author><name sortKey="Aquilano, K" uniqKey="Aquilano K">K. Aquilano</name></author><author><name sortKey="De Chiara, G" uniqKey="De Chiara G">G. De Chiara</name></author><author><name sortKey="Hernandez, L" uniqKey="Hernandez L">L. Hernandez</name></author><author><name sortKey="Cozzolino, F" uniqKey="Cozzolino F">F. Cozzolino</name></author><author><name sortKey="Ciriolo, M R" uniqKey="Ciriolo M">M.R. Ciriolo</name></author><author><name sortKey="Garaci, E" uniqKey="Garaci E">E. Garaci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Y L" uniqKey="Huang Y">Y.L. Huang</name></author><author><name sortKey="Loke, S H" uniqKey="Loke S">S.H. Loke</name></author><author><name sortKey="Hsu, C C" uniqKey="Hsu C">C.C. Hsu</name></author><author><name sortKey="Chiou, W F" uniqKey="Chiou W">W.F. Chiou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Y L" uniqKey="Huang Y">Y.L. Huang</name></author><author><name sortKey="Tsai, W J" uniqKey="Tsai W">W.J. Tsai</name></author><author><name sortKey="Shen, C C" uniqKey="Shen C">C.C. Shen</name></author><author><name sortKey="Chen, C C" uniqKey="Chen C">C.C. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia Alonso, M" uniqKey="Garcia Alonso M">M. García-Alonso</name></author><author><name sortKey="Rimbach, G" uniqKey="Rimbach G">G. Rimbach</name></author><author><name sortKey="Rivas Gonzalo, J C" uniqKey="Rivas Gonzalo J">J.C. Rivas-Gonzalo</name></author><author><name sortKey="De Pascual Teresa, S" uniqKey="De Pascual Teresa S">S. De Pascual-Teresa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, K S" uniqKey="Huang K">K.S. Huang</name></author><author><name sortKey="Lin, M" uniqKey="Lin M">M. Lin</name></author><author><name sortKey="Cheng, G F" uniqKey="Cheng G">G.F. Cheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Y L" uniqKey="Huang Y">Y.L. Huang</name></author><author><name sortKey="Loke, S H" uniqKey="Loke S">S.H. Loke</name></author><author><name sortKey="Hsu, C C" uniqKey="Hsu C">C.C. Hsu</name></author><author><name sortKey="Chiou, W F" uniqKey="Chiou W">W.F. Chiou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Germouty, J" uniqKey="Germouty J">J. Germouty</name></author><author><name sortKey="Jirou Najou, J L" uniqKey="Jirou Najou J">J.L. Jirou-Najou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yang, B" uniqKey="Yang B">B. Yang</name></author><author><name sortKey="Yao, D F" uniqKey="Yao D">D.F. Yao</name></author><author><name sortKey="Ohuchi, M" uniqKey="Ohuchi M">M. Ohuchi</name></author><author><name sortKey="Ide, M" uniqKey="Ide M">M. Ide</name></author><author><name sortKey="Yano, M" uniqKey="Yano M">M. Yano</name></author><author><name sortKey="Okumura, Y" uniqKey="Okumura Y">Y. Okumura</name></author><author><name sortKey="Kido, H" uniqKey="Kido H">H. Kido</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gillissen, A" uniqKey="Gillissen A">A. Gillissen</name></author><author><name sortKey="Bartling, A" uniqKey="Bartling A">A. Bartling</name></author><author><name sortKey="Schoen, S" uniqKey="Schoen S">S. Schoen</name></author><author><name sortKey="Schultze Werninghaus, G" uniqKey="Schultze Werninghaus G">G. Schultze-Werninghaus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gillissen, A" uniqKey="Gillissen A">A. Gillissen</name></author><author><name sortKey="Sch Rling, B" uniqKey="Sch Rling B">B. Schärling</name></author><author><name sortKey="Jaworska, M" uniqKey="Jaworska M">M. Jaworska</name></author><author><name sortKey="Bartling, A" uniqKey="Bartling A">A. Bartling</name></author><author><name sortKey="Rasche, K" uniqKey="Rasche K">K. Rasche</name></author><author><name sortKey="Schultze Werninghaus, G" uniqKey="Schultze Werninghaus G">G. Schultze-Werninghaus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nobata, K" uniqKey="Nobata K">K. Nobata</name></author><author><name sortKey="Fujimura, M" uniqKey="Fujimura M">M. Fujimura</name></author><author><name sortKey="Ishiura, Y" uniqKey="Ishiura Y">Y. Ishiura</name></author><author><name sortKey="Myou, S" uniqKey="Myou S">S. Myou</name></author><author><name sortKey="Nakao, S" uniqKey="Nakao S">S. Nakao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tsujimoto, Y" uniqKey="Tsujimoto Y">Y. Tsujimoto</name></author><author><name sortKey="Hashizume, H" uniqKey="Hashizume H">H. Hashizume</name></author><author><name sortKey="Yamazaki, M" uniqKey="Yamazaki M">M. Yamazaki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jariwalla, R J" uniqKey="Jariwalla R">R.J. Jariwalla</name></author><author><name sortKey="Roomi, M W" uniqKey="Roomi M">M.W. Roomi</name></author><author><name sortKey="Gangapurkar, B" uniqKey="Gangapurkar B">B. Gangapurkar</name></author><author><name sortKey="Kalinovsky, T" uniqKey="Kalinovsky T">T. Kalinovsky</name></author><author><name sortKey="Niedzwiecki, A" uniqKey="Niedzwiecki A">A. Niedzwiecki</name></author><author><name sortKey="Rath, M" uniqKey="Rath M">M. Rath</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Furuya, A" uniqKey="Furuya A">A. Furuya</name></author><author><name sortKey="Uozaki, M" uniqKey="Uozaki M">M. Uozaki</name></author><author><name sortKey="Yamasaki, H" uniqKey="Yamasaki H">H. Yamasaki</name></author><author><name sortKey="Arakawa, T" uniqKey="Arakawa T">T. Arakawa</name></author><author><name sortKey="Arita, M" uniqKey="Arita M">M. Arita</name></author><author><name sortKey="Koyama, A H" uniqKey="Koyama A">A.H. Koyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kimbarowski, J A" uniqKey="Kimbarowski J">J.A. Kimbarowski</name></author><author><name sortKey="Mokrow, N J" uniqKey="Mokrow N">N.J. Mokrow</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banerjee, D" uniqKey="Banerjee D">D. Banerjee</name></author><author><name sortKey="Kaul, D" uniqKey="Kaul D">D. Kaul</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robak, J" uniqKey="Robak J">J. Robak</name></author><author><name sortKey="Gryglewski, R J" uniqKey="Gryglewski R">R.J. Gryglewski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Miyaichi, Y" uniqKey="Miyaichi Y">Y. Miyaichi</name></author><author><name sortKey="Tomimori, T" uniqKey="Tomimori T">T. Tomimori</name></author><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Miyaichi, Y" uniqKey="Miyaichi Y">Y. Miyaichi</name></author><author><name sortKey="Tomimori, T" uniqKey="Tomimori T">T. Tomimori</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Miyaichi, Y" uniqKey="Miyaichi Y">Y. Miyaichi</name></author><author><name sortKey="Tomimori, T" uniqKey="Tomimori T">T. Tomimori</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author><author><name sortKey="Tomimori, T" uniqKey="Tomimori T">T. Tomimori</name></author><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nagai, T" uniqKey="Nagai T">T. Nagai</name></author><author><name sortKey="Moriguchi, R" uniqKey="Moriguchi R">R. Moriguchi</name></author><author><name sortKey="Suzuki, Y" uniqKey="Suzuki Y">Y. Suzuki</name></author><author><name sortKey="Tomimori, T" uniqKey="Tomimori T">T. Tomimori</name></author><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Song, J M" uniqKey="Song J">J.M. Song</name></author><author><name sortKey="Lee, K H" uniqKey="Lee K">K.H. Lee</name></author><author><name sortKey="Seong, B L" uniqKey="Seong B">B.L. Seong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kashima, M" uniqKey="Kashima M">M. Kashima</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yamada, H" uniqKey="Yamada H">H. Yamada</name></author><author><name sortKey="Takuma, N" uniqKey="Takuma N">N. Takuma</name></author><author><name sortKey="Daimon, T" uniqKey="Daimon T">T. Daimon</name></author><author><name sortKey="Hara, Y" uniqKey="Hara Y">Y. Hara</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mori, S" uniqKey="Mori S">S. Mori</name></author><author><name sortKey="Miyake, S" uniqKey="Miyake S">S. Miyake</name></author><author><name sortKey="Kobe, T" uniqKey="Kobe T">T. Kobe</name></author><author><name sortKey="Nakaya, T" uniqKey="Nakaya T">T. Nakaya</name></author><author><name sortKey="Fuller, S D" uniqKey="Fuller S">S.D. Fuller</name></author><author><name sortKey="Kato, N" uniqKey="Kato N">N. Kato</name></author><author><name sortKey="Kaihatsu, K" uniqKey="Kaihatsu K">K. Kaihatsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuzuhara, T" uniqKey="Kuzuhara T">T. Kuzuhara</name></author><author><name sortKey="Iwai, Y" uniqKey="Iwai Y">Y. Iwai</name></author><author><name sortKey="Takahashi, H" uniqKey="Takahashi H">H. Takahashi</name></author><author><name sortKey="Hatakeyama, D" uniqKey="Hatakeyama D">D. Hatakeyama</name></author><author><name sortKey="Echigo, N" uniqKey="Echigo N">N. Echigo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, H J" uniqKey="Choi H">H.J. Choi</name></author><author><name sortKey="Song, J H" uniqKey="Song J">J.H. Song</name></author><author><name sortKey="Park, K S" uniqKey="Park K">K.S. Park</name></author><author><name sortKey="Kwon, D H" uniqKey="Kwon D">D.H. Kwon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Narayanan, S" uniqKey="Narayanan S">S. Narayanan</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.O. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujii, H" uniqKey="Fujii H">H. Fujii</name></author><author><name sortKey="Sun, B" uniqKey="Sun B">B. Sun</name></author><author><name sortKey="Nishioka, H" uniqKey="Nishioka H">H. Nishioka</name></author><author><name sortKey="Hirose, A" uniqKey="Hirose A">A. Hirose</name></author><author><name sortKey="Aruoma, O I" uniqKey="Aruoma O">O.I. Aruoma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gangehei, L" uniqKey="Gangehei L">L. Gangehei</name></author><author><name sortKey="Ali, M" uniqKey="Ali M">M. Ali</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W. Zhang</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z. Chen</name></author><author><name sortKey="Wakame, K" uniqKey="Wakame K">K. Wakame</name></author><author><name sortKey="Haidari, M" uniqKey="Haidari M">M. Haidari</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">Molecules</journal-id><journal-id journal-id-type="iso-abbrev">Molecules</journal-id><journal-id journal-id-type="publisher-id">molecules</journal-id><journal-title-group><journal-title>Molecules</journal-title></journal-title-group><issn pub-type="epub">1420-3049</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21358592</article-id><article-id pub-id-type="pmc">6259602</article-id><article-id pub-id-type="doi">10.3390/molecules23100000</article-id><article-id pub-id-type="publisher-id">molecules-16-02032</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Uchide</surname><given-names>Noboru</given-names></name><xref rid="c1-molecules-16-02032" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Toyoda</surname><given-names>Hiroo</given-names></name></contrib></contrib-group><aff id="af1-molecules-16-02032">Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan</aff><author-notes><corresp id="c1-molecules-16-02032"><label>*</label>Author to whom correspondence should be addressed; E-Mail: <email>uchide@toyaku.ac.jp</email>; Tel.: +81 42 676 5760; Fax: +81 42 676 5738.</corresp></author-notes><pub-date pub-type="epub"><day>28</day><month>2</month><year>2011</year></pub-date><pub-date pub-type="collection"><month>3</month><year>2011</year></pub-date><volume>16</volume><issue>3</issue><fpage>2032</fpage><lpage>2052</lpage><history><date date-type="received"><day>10</day><month>2</month><year>2011</year></date><date date-type="rev-recd"><day>23</day><month>2</month><year>2011</year></date><date date-type="accepted"><day>25</day><month>2</month><year>2011</year></date></history><permissions><copyright-statement>© 2011 by the authors;</copyright-statement><copyright-year>2011</copyright-year><license license-type="open-access"><license-p>licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>).</license-p></license></permissions><abstract><p>With the appearance of the novel influenza A (H1N1) virus 2009 strain we have experienced a new influenza pandemic and many patients have died from severe complications associated with this pandemic despite receiving intensive care. This suggests that a definitive medical treatment for severe influenza-associated complications has not yet been established. Many studies have shown that superoxide anion produced by macrophages infiltrated into the virus-infected organs is implicated in the development of severe influenza-associated complications. Selected antioxidants, such as pyrrolidine dithiocabamate, <italic>N</italic>-acetyl-<sc>l</sc>-cysteine, glutathione, nordihydroguaiaretic acid, thujaplicin, resveratrol, (+)-vitisin A, ambroxol, ascorbic acid, 5,7,4-trihydroxy-8-methoxyflavone, catechins, quercetin 3-rhamnoside, iso- quercetin and oligonol, inhibit the proliferation of influenza virus and scavenge superoxide anion. The combination of antioxidants with antiviral drugs synergistically reduces the lethal effects of influenza virus infections. These results suggest that an agent with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with severe influenza-associated complications. This review article updates knowledge of antioxidant therapy as a potential approach to severe influenza-associated complications.</p></abstract><kwd-group><kwd>antioxidant</kwd><kwd>influenza</kwd><kwd>antiviral drug</kwd></kwd-group></article-meta></front><body><sec id="sec1-molecules-16-02032"><title>1. Introduction</title><p>With the appearance of the novel influenza A (H1N1) virus 2009 strain we have recently experienced a new influenza pandemic [<xref rid="B1-molecules-16-02032" ref-type="bibr">1</xref>,<xref rid="B2-molecules-16-02032" ref-type="bibr">2</xref>]. The clinical spectrum of pandemic influenza A (H1N1) virus infection was broad, ranging from mild upper respiratory tract illness with or without fever and occasional gastrointestinal symptoms such as vomiting or diarrhea and exacerbation of underlying conditions, to severe complications such as pneumonia resulting in respiratory failure, acute respiratory distress syndrome, multi-organ failure and even death [<xref rid="B3-molecules-16-02032" ref-type="bibr">3</xref>,<xref rid="B4-molecules-16-02032" ref-type="bibr">4</xref>]. Many patients died from severe complications associated with the pandemic influenza A (H1N1) virus infection despite receiving intensive care [<xref rid="B3-molecules-16-02032" ref-type="bibr">3</xref>,<xref rid="B4-molecules-16-02032" ref-type="bibr">4</xref>], and as of the 25<sup>th</sup> of July 2010, 18,398 laboratory-confirmed fatal cases of pandemic influenza A (H1N1) have been reported to the World Health Organization [<xref rid="B5-molecules-16-02032" ref-type="bibr">5</xref>]. The influenza A (H1N1) virus human infections event has now moved into a post-pandemic period, with a pattern that has been transitioning towards that of seasonal influenza [<xref rid="B6-molecules-16-02032" ref-type="bibr">6</xref>]. Beside the influenza A (H1N1) pandemic the global burden of seasonal influenza epidemics is believed to be some 3-5 million cases of severe illness and 300,000–500,000 deaths every year [<xref rid="B7-molecules-16-02032" ref-type="bibr">7</xref>]. Additionally, we still face the threat of infection with the highly pathogenic avian influenza A (H5N1) virus.</p><p>Three classes of anti-influenza drugs have been used for chemoprophylaxis and treatment of influenza virus infections [<xref rid="B8-molecules-16-02032" ref-type="bibr">8</xref>] (<xref ref-type="fig" rid="molecules-16-02032-f001">Figure 1</xref>): amantadine (<bold>1</bold>) and rimantadine (<bold>2</bold>) which inhibit viral membrane protein (M2) of the proton channel that is necessary for uncoating; oseltamivir (<bold>3</bold>), zanamivir (<bold>4</bold>), peramivir (<bold>5</bold>) and laninamivir octanoate (<bold>6</bold>) which inhibit viral neuraminidase (NA) that is necessary for virion release and ribavirin (<bold>7</bold>) that inhibits enzyme activity essential for viral replication. Initial diagnostic testing found that the pandemic influenza A (H1N1) virus was susceptible to NA inhibitors, but resistant to M2 inhibitors [<xref rid="B9-molecules-16-02032" ref-type="bibr">9</xref>], therefore, oseltamivir has been used widely for treatment and chemoprophylaxis of pandemic influenza A (H1N1) [<xref rid="B2-molecules-16-02032" ref-type="bibr">2</xref>]. Sporadic cases of oseltamivir-resistant pandemic influenza A (H1N1) virus have been reported worldwide [<xref rid="B10-molecules-16-02032" ref-type="bibr">10</xref>]. This oseltamivir resistance was caused by the NA mutation H275Y [<xref rid="B10-molecules-16-02032" ref-type="bibr">10</xref>]. Person-to-person transmission of oseltamivir-resistant viruses in healthy adults has been confirmed [<xref rid="B11-molecules-16-02032" ref-type="bibr">11</xref>]. In cases of development of oseltamivir-resistance, treatment options are limited because zanamivir is not licensed for treatment of children under 7 years old and is contraindicated in persons with underlying airway disease. Recently, it has been reported that a single inhalation of laninamivir octanoate was an effective and well-tolerated drug for the treatment of children with oseltamivir-resistant influenza A (H1N1) virus infection [<xref rid="B12-molecules-16-02032" ref-type="bibr">12</xref>]. Additionally, intravenous drip infusion of peramivir has offered a new treatment option for children and infants suffering from influenza virus infections and patients where oral administration was difficult or not possible [<xref rid="B13-molecules-16-02032" ref-type="bibr">13</xref>]. It was also effective for severe influenza-associated complications, such as acute respiratory failure [<xref rid="B14-molecules-16-02032" ref-type="bibr">14</xref>]. Nonetheless, NA inhibitor-resistant viruses with H275Y mutation emerged early and replicated in patients, who have received hematopoietic cell transplant, under treatment with immunosuppressive drugs after intravenous drip infusion of peramivir [<xref rid="B15-molecules-16-02032" ref-type="bibr">15</xref>]. A young adult with pandemic influenza A (H1N1) virus infection was treated with intravenous peramivir, but died from severe viral pneumonia [<xref rid="B16-molecules-16-02032" ref-type="bibr">16</xref>]. These results suggest the need for development of new anti-influenza drugs utilizing alternative antiviral mechanisms and consideration of using anti-influenza drug combinations. Some such approaches have been explored, whereby a triple combination of amantadine, ribavirin and oseltamivir was highly active and synergistic against drug resistant influenza virus strains <italic>in vitro</italic> [<xref rid="B17-molecules-16-02032" ref-type="bibr">17</xref>]. </p><p>In cases of severe influenza-associated complications, the pathological manifestations are the result of complex biological phenomena, such as apoptosis induction, macrophage activation, oxidative tissue damage and higher contents of pro-inflammatory cytokines [<xref rid="B18-molecules-16-02032" ref-type="bibr">18</xref>]. The pathogenesis of severe influenza-associated complications involves not only apoptotic cell death mediated through virus replication in the infected cells, but also the injury of non-infected cells by superoxide anion derived from activated phagocytes (<italic>i.e.</italic>, macrophages and neutrophils) infiltrated into the virus-infected organs [<xref rid="B19-molecules-16-02032" ref-type="bibr">19</xref>]. As illustrated in <xref ref-type="fig" rid="molecules-16-02032-f002">Figure 2</xref> [<xref rid="B19-molecules-16-02032" ref-type="bibr">19</xref>], host cells secrete cysteine-cysteine (C-C) chemokines that primarily target monocytes [e.g., monocyte chemoattractant protein (MCP)-1, regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein (MIP)-1α/β) and monocyte differentiation-inducing (MDI) factor (<italic>i.e.</italic>, interleukin (IL)-6, tumor necrosis factor (TNF)-α and interferon (IFN)-β] in response to influenza virus replication prior to undergoing apoptotic cell degradation. The C-C chemokines act on immature monocytes circulating in the bloodstream, recruiting them to the site of infection. The MDI factor acts on the recruited monocytes, resulting in differentiation into well-matured macrophages capable of phagocytosing and producing superoxide anion. The activated macrophages move to the virus- infected host cell and phagocytose apoptotic cell debris resulting from the viral infection. An abrupt increase in superoxide anion production occurs during phagocytosis. This superoxide anion induces injuries in non-infected cells. These superoxide anion-mediated pathways represent a part of the mechanisms of extensive tissue injury observed during severe influenza-associated complications [<xref rid="B20-molecules-16-02032" ref-type="bibr">20</xref>], therefore, it has been suggested that an agent with antiviral and antioxidant activities could be a drug of choice for the treatment of patients with such severe complications [<xref rid="B21-molecules-16-02032" ref-type="bibr">21</xref>,<xref rid="B22-molecules-16-02032" ref-type="bibr">22</xref>]. This review article updates knowledge of antioxidant therapy as a potential approach to these severe influenza-associated complications.</p></sec><sec id="sec2-molecules-16-02032"><title>2. Effect of Selected Antioxidants on the Pathogenesis of Influenza Virus Infections</title><sec id="sec2dot1-molecules-16-02032"><title>2.1. Superoxide dismutases</title><p>Intravenous injection of pyran polymer conjugated with copper/zinc (Cu/Zn)-superoxide dismutase (SOD) protected mice against a potentially lethal influenza virus infection [<xref rid="B23-molecules-16-02032" ref-type="bibr">23</xref>]. Intravenous injection of manganese (Mn)-SOD to mice with influenza virus infection at a lethal dose mildly increased mean days of survival, lessened arterial oxygen saturation decline, and lowered lung consolidation [<xref rid="B24-molecules-16-02032" ref-type="bibr">24</xref>]. A combination of Mn-SOD and ribavirin, each of which was administered as a small-particle aerosol, resulted in a generally mild improvement of the disease induced by the influenza A virus, compared with use of either substance alone [<xref rid="B24-molecules-16-02032" ref-type="bibr">24</xref>]. A combined application of Cu/Zn-SOD and rimantadine hydrochloride in doses which by themselves did not protect significantly mice against the infection, resulted in a synergistic decrease in lung virus titers, lung weights and consolidation and mortality rates [<xref rid="B25-molecules-16-02032" ref-type="bibr">25</xref>]. Treatment with allopurinol, an inhibitor of xanthine oxidase capable of generating superoxide anion, improved the survival rate of influenza virus-infected mice [<xref rid="B26-molecules-16-02032" ref-type="bibr">26</xref>]. It should be noted that the treatment with SODs decreased the lethal or toxic effect of influenza virus infection in mouse models, but did not inhibit the virus proliferation [<xref rid="B23-molecules-16-02032" ref-type="bibr">23</xref>,<xref rid="B24-molecules-16-02032" ref-type="bibr">24</xref>,<xref rid="B25-molecules-16-02032" ref-type="bibr">25</xref>,<xref rid="B26-molecules-16-02032" ref-type="bibr">26</xref>]. Transgenic mice carrying overexpressed extracellular SOD exhibited less severe lung injury after influenza virus infection [<xref rid="B27-molecules-16-02032" ref-type="bibr">27</xref>]. Mice lacking functional phagocyte NADPH oxidase capable of generating superoxide anion exhibited an increase of macrophages and the reduction of apoptosis in macrophages and virus titer in the bronchoalveolar space after influenza virus infection, as compared to those of wild-type animals [<xref rid="B28-molecules-16-02032" ref-type="bibr">28</xref>]. Therefore, these studies suggest that superoxide anion produced by phagocytes, especially macrophages, plays a critical role in the pathogenesis of influenza virus infections. Since SODs do not inhibit the proliferation of influenza virus, an agent possessing both antiviral and antioxidant activities would be desirable for antioxidant therapy as a new approach to severe influenza-associated complications.</p></sec><sec id="sec2dot2-molecules-16-02032"><title>2.2. Thiol antioxidants</title><sec id="sec2dot2dot1-molecules-16-02032"><title>2.2.1. Pyrrolidine dithiocarbamate</title><p>Pyrrolidine dithiocarbamate (PDTC, <bold>8</bold>, <xref ref-type="fig" rid="molecules-16-02032-f003">Figure 3</xref>) has been shown to scavenge hydroxyl and superoxide anion radicals; its effect is comparable to that of other free radical scavengers, such as ascorbate and glutathione [<xref rid="B29-molecules-16-02032" ref-type="bibr">29</xref>]. Both PDTC and Trolox<sup>®</sup> (6-hydroxy-2,5,7,8-tetra- methylchroman-2-carboxylic acid; a water-soluble vitamin E analogue) suppressed the accumulation of reactive oxygen species (ROS) in chorion cells caused by influenza virus infection [<xref rid="B30-molecules-16-02032" ref-type="bibr">30</xref>,<xref rid="B31-molecules-16-02032" ref-type="bibr">31</xref>]. PDTC inhibited both apoptosis induction and virus proliferation in the infected chorion cells, whereas no such inhibitory effect was observed with Trolox<sup>®</sup> [<xref rid="B30-molecules-16-02032" ref-type="bibr">30</xref>,<xref rid="B31-molecules-16-02032" ref-type="bibr">31</xref>]. PDTC also inhibited the cytopathic effect of influenza virus infection on the other types of cells, such as human pulmonary epithelial A549 cells and murine macrophage J774.1 cells [<xref rid="B32-molecules-16-02032" ref-type="bibr">32</xref>,<xref rid="B33-molecules-16-02032" ref-type="bibr">33</xref>,<xref rid="B34-molecules-16-02032" ref-type="bibr">34</xref>]. Studies using J774.1 cells also demonstrated that various other antioxidants, such as Trolox<sup>®</sup>, deferoximine nesyiate, dithiothreitol, <italic>N</italic>-methyl-D-arginine, catalase and SOD, did not inhibit the cytopathic effects of influenza virus infection [<xref rid="B33-molecules-16-02032" ref-type="bibr">33</xref>,<xref rid="B34-molecules-16-02032" ref-type="bibr">34</xref>]. These results suggest that the inhibition of influenza virus-induced apoptosis by PDTC is attributable to its antiviral activity rather than its antioxidant properties. That is, ROS may not be responsible for apoptosis induction by influenza virus infection [<xref rid="B30-molecules-16-02032" ref-type="bibr">30</xref>,<xref rid="B31-molecules-16-02032" ref-type="bibr">31</xref>]. However, as described in the previous section, it has been suggested that organ injury was occurred by ROS derived from phagocytes during influenza virus infection in mouse models. Therefore, these evidence reveals that the pathogenesis of influenza virus infection involves not only the virus replication-mediated apoptotic cell death in the infected cells irrespective of ROS, but also the injury of non-infected cells by ROS derived from macrophages and neutrophils infiltrated into the virus-infected organs. The findings support the notion that an agent with antiviral and antioxidant activities can be a drug of choice for the treatment of patients with severe influenza-associated complications and that PDTC could be one of these drug candidates. Since PDTC is well tolerated <italic>in vivo</italic> at doses of up to 100 mg/kg (intraperitoneal injection) and exhibits therapeutic effects on animal inflammation and tissue injury models [<xref rid="B35-molecules-16-02032" ref-type="bibr">35</xref>,<xref rid="B36-molecules-16-02032" ref-type="bibr">36</xref>,<xref rid="B37-molecules-16-02032" ref-type="bibr">37</xref>,<xref rid="B38-molecules-16-02032" ref-type="bibr">38</xref>], further studies on the therapeutic effect of PDTC on animal influenza models are warranted.</p><p>The mode of inhibitory effect of PDTC on influenza virus proliferation has been investigated. PDTC inhibited the synthesis of negative-strand virion RNA (vRNA) and positive-strand complementary and/or messenger RNA (c/mRNA) for influenza virus HA gene in the infected cells [<xref rid="B31-molecules-16-02032" ref-type="bibr">31</xref>], therefore it is likely that the inhibition of influenza virus gene replication and transcription contributes to the inhibition of virus proliferation. Dithiocarbamates can chelate various divalent metal ions, leading to the formation of lipophilic dithiocarbamate-metal complexes, and rapid transport via a lipophilic complex by PDTC has been proposed to explain the intracellular recruitment of copper and zinc ions from the extracellular medium [<xref rid="B39-molecules-16-02032" ref-type="bibr">39</xref>]. It has been demonstrated that copper and zinc ions inhibit influenza virus RNA-dependent RNA polymerase activity, and that the inhibitory effect of bathocuproine-copper and batho- cuproine-zinc complexes is greater than that of bathocuproine itself [<xref rid="B40-molecules-16-02032" ref-type="bibr">40</xref>]. Moreover, it has been known that PDTC-copper and PDTC-zinc complexes (<bold>9</bold> and <bold>10</bold>, respectively, <xref ref-type="fig" rid="molecules-16-02032-f003">Figure 3</xref>) inhibited the replication of Coxsackie virus [<xref rid="B41-molecules-16-02032" ref-type="bibr">41</xref>] and rhinovirus [<xref rid="B42-molecules-16-02032" ref-type="bibr">42</xref>]. Conceivably, PDTC may inhibit influenza virus gene replication and transcription through the inhibition of viral RNA-dependent RNA polymerase activity by increasing the amount of intracellular copper and zinc ions or intracellular PDTC-copper and PDTC-zinc complexes, but further study is needed to elucidate the precise mechanism of inhibitory effect of PDTC on influenza virus gene replication and transcription.</p><p>Furthermore, it has been revealed that PDTC inhibited the induction of gene expression for MDI factors and C-C chemokines, such as IL-6, TNF-α, IFN-β and RANTES, by influenza virus infection [<xref rid="B43-molecules-16-02032" ref-type="bibr">43</xref>,<xref rid="B44-molecules-16-02032" ref-type="bibr">44</xref>, our unpublished data]. Consequently, PDTC may attenuate the activation of macrophages during influenza virus infection via a suppressive effect on production of cytokines, thus reducing the pathogenesis of influenza virus infections.</p></sec><sec id="sec2dot2dot2-molecules-16-02032"><title>2.2.2. <italic>N</italic>-Acetyl-<sc>l</sc>-cysteine</title><p><italic>N</italic>-Acetyl-<sc>l</sc>-cysteine (NAC, <bold>11</bold>, <xref ref-type="fig" rid="molecules-16-02032-f003">Figure 3</xref>), the acetylated derivative of the amino acid <sc>l</sc>-cysteine, is an excellent source of thiol groups, and is converted in the body into metabolites capable of stimulating glutathione synthesis, promoting detoxification, and acting directly as free radical scavengers [<xref rid="B45-molecules-16-02032" ref-type="bibr">45</xref>]. NAC inhibited the induction of apoptosis [<xref rid="B46-molecules-16-02032" ref-type="bibr">46</xref>,<xref rid="B47-molecules-16-02032" ref-type="bibr">47</xref>,<xref rid="B48-molecules-16-02032" ref-type="bibr">48</xref>] and gene expression for pro-inflammatory cytokines and chemokines such as IL-6, IL-8, RANTES and interferon-inducing protein (IP)-10, by influenza virus infection [<xref rid="B48-molecules-16-02032" ref-type="bibr">48</xref>]. NAC inhibited the proliferation of influenza virus at an early, but not later, stage of infection [<xref rid="B47-molecules-16-02032" ref-type="bibr">47</xref>,<xref rid="B48-molecules-16-02032" ref-type="bibr">48</xref>]. Administration of NAC significantly decreased the mortality in mice infected with influenza virus [<xref rid="B49-molecules-16-02032" ref-type="bibr">49</xref>], and a combination of NAC and ribavirin synergistically reduced the lethal effects [<xref rid="B50-molecules-16-02032" ref-type="bibr">50</xref>]. Furthermore, a combination of NAC and oseltamivir also synergistically reduced the lethal effect of influenza virus infection in mice [<xref rid="B51-molecules-16-02032" ref-type="bibr">51</xref>]. These results support the notion that combinations of antioxidant therapy with current drugs can improve the treatment of influenza virus infections.</p><p>Administration of NAC appears to reduce symptomatic conditions associated with influenza virus infection. A total of 262 subjects of both sexes were given either placebo or NAC (600 mg) orally twice daily for six months. Although incidents of seroconversion towards A (H1N1) Singapore 6/86 influenza virus was similar in the two groups, NAC treatment decreased both the incidence and severity of influenza-like episodes, and the length of time confined to bed. The authors concluded that NAC did not prevent influenza A (H1N1) virus infection, but did significantly reduce the incidence of clinically apparent disease [<xref rid="B52-molecules-16-02032" ref-type="bibr">52</xref>]. In another paper, it has been reported that a patient with viral pneumonia caused by the novel influenza A (H1N1) virus 2009 infection and septic shock improved rapidly after continuous intravenous infusion of high-dose NAC at 100 mg/kg combined with oseltamivir [<xref rid="B53-molecules-16-02032" ref-type="bibr">53</xref>]. </p></sec><sec id="sec2dot2dot3-molecules-16-02032"><title>2.2.3. Glutathione</title><p>Reduced glutathione (<bold>12</bold>, <xref ref-type="fig" rid="molecules-16-02032-f003">Figure 3</xref>) displays anti-influenza activity <italic>in vitro</italic> and <italic>in vivo</italic> [<xref rid="B54-molecules-16-02032" ref-type="bibr">54</xref>]. The addition of reduced glutathione into culture medium exogenously blocked the induction of apoptosis through the inhibition of viral macromolecule synthesis in Madin-Darby canine kidney (MDCK) cells after influenza virus infection. The antiviral effect of reduced glutathione on influenza virus proliferation was also observed in normal human small airway epithelial cells. In BALB/c mice, inclusion of reduced glutathione in the drinking water decreased viral titer in both lung and trachea homogenates at 4 days after intranasal inoculation with a mouse-adopted influenza strain A/X-31. Moreover, both the levels of Bcl-2 expression and the content of intracellular reduced glutathione contribute to the ability of host cells for down-regulating influenza virus replication, although their effects are exerted at different stages of the viral life-cycle [<xref rid="B55-molecules-16-02032" ref-type="bibr">55</xref>].</p></sec></sec><sec id="sec2dot3-molecules-16-02032"><title>2.3. Hydroxyl antioxidants</title><sec id="sec2dot3dot1-molecules-16-02032"><title>2.3.1. Nordihydroguaiaretic acid</title><p>Nordihydroguaiaretic acid [1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane, NDGA, <bold>13</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>] occurs in the resinous exudates of the creosote bush <italic>Larrea divaricata</italic>. NDGA scavenges oxygen radicals, such as peroxynitrite, singlet oxygen, hydroxyl and superoxide anion radicals [<xref rid="B56-molecules-16-02032" ref-type="bibr">56</xref>]. The ability of NDGA to scavenge the above-mentioned oxygen radicals is much greater than that of reference tested compounds, such as uric acid, penicillamine, reduced glutathione and mannitol [<xref rid="B56-molecules-16-02032" ref-type="bibr">56</xref>]. These strong antioxidant properties may be due to the presence of four reducing equivalents from the two catechol groups in NDGA; hydrogen atoms of the four phenolic hydroxyl groups react with oxygen radicals [<xref rid="B56-molecules-16-02032" ref-type="bibr">56</xref>]. NDGA has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders, cancers and virus infections [<xref rid="B57-molecules-16-02032" ref-type="bibr">57</xref>]. The treatment with NDGA inhibited apoptotic DNA fragmentation and virus proliferation in chorion cells infected with influenza virus [<xref rid="B58-molecules-16-02032" ref-type="bibr">58</xref>]. Erimos Pharmaceuticals, in collaboration with researchers at North Carolina State University (NCSU), has shown potential benefits of terameprocol (tetra-<italic>O</italic>-methyl NDGA, <bold>14</bold><xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>) [<xref rid="B59-molecules-16-02032" ref-type="bibr">59</xref>] in treating pneumonia and other symptoms related to influenza virus infection. Eads and co-workers in NCSA have demonstrated the inhibitory effect of terameprocol on prostaglandin E<sub>2</sub> production in macrophages infected with influenza virus [<xref rid="B60-molecules-16-02032" ref-type="bibr">60</xref>].</p><p>Recently, it has been reported that several methylated derivatives of NDGA possessed an inhibitory activity on the expression of reporter genes driven by some viral promoters of herpes simplex virus, human papillomavirus and human immunodeficiency virus, which was resulting from the inhibitory effect on the binding of cellular transcription factor Sp-1 to viral gene promoters [<xref rid="B61-molecules-16-02032" ref-type="bibr">61</xref>]. </p><p>NDGA derivatives did not affect the expression of reporter genes driven by the adenovirus major late promoter and the cytomegalovirus promoter [<xref rid="B61-molecules-16-02032" ref-type="bibr">61</xref>]. It is predicted that the antiviral activity of NDGA derivatives is selective, depending on the virus types. Influenza virus has viral RNA-dependent RNA polymerases, which contribute to the replication and transcription processes of the viral genes, probably irrespective of cellular transcription factor Sp-1. An additional mechanism of NDGA for the inhibition of influenza virus proliferation has been proposed. NDGA is shown to inhibit the intracellular transport of vesicular stomatitis virus glycoproteins [<xref rid="B62-molecules-16-02032" ref-type="bibr">62</xref>]. Conceivably, NDGA may inhibit influenza virus proliferation via inhibition of intracellular transport of viral glycoproteins.</p></sec><sec id="sec2dot3dot2-molecules-16-02032"><title>2.3.2. Thujaplicin</title><p>The thujaplicins, including α-thujaplicin (2-hydroxy-3-isopropyl-2,4,6-cycloheptatrien-1- one), β-thujaplicin (2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1-one) and γ-thujaplicin (2-hydroxy-5-isopropyl-2,4,6-cycloheptatrien-1-one) (<bold>15</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>), are tropolone-related compounds found in the heartwood of several cupressaceous plants, such as Western Red Cedar (<italic>Thuja plicata</italic>), Eastern White Cedar (<italic>Thuja occidentalis</italic>) and Hinoki Cypress (<italic>Chamaecryprais obtusa</italic>) [<xref rid="B63-molecules-16-02032" ref-type="bibr">63</xref>]. Copper complexes of α-, β- and γ-thujaplicin blocked the induction of apoptosis in MDCK cells by influenza virus infection through their antiviral effects, while their ferrous, ferric, magnesium and manganese complexes showed no inhibition of influenza virus-induced apoptosis [<xref rid="B64-molecules-16-02032" ref-type="bibr">64</xref>]. Thujaplicin scavenges hydroxyl radical, <italic>tert</italic>-butyl peroxyl radical, hydrogen peroxide, superoxide anion radical and singlet oxygen [<xref rid="B65-molecules-16-02032" ref-type="bibr">65</xref>].</p></sec><sec id="sec2dot3dot3-molecules-16-02032"><title>2.3.3. Resveratrol</title><p>The plant polyphenol resveratorol (3,5,4’-trihydroxy-<italic>trans</italic>-stilbene) (<bold>16</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>) inhibited the progressive effects of superoxide anion and hydrogen peroxide radicals on arachidonic acid production and cyclooxygenase-2 induction in macrophages [<xref rid="B66-molecules-16-02032" ref-type="bibr">66</xref>]. Resveratrol inhibited the replication of influenza virus in MDCK cells, as a result of the blockade of the nuclear- cytoplasmic translocation of viral ribonucleoproteins and the reduced expression of late viral protein, such as HA and matrix protein [<xref rid="B67-molecules-16-02032" ref-type="bibr">67</xref>]. Resveratol also improved survival and decreased pulmonary viral titers in influenza virus-infected mice [<xref rid="B67-molecules-16-02032" ref-type="bibr">67</xref>]. Since resveratrol inhibited the induction of RANTES production by influenza virus infection in A549 lung epithelial cells [<xref rid="B68-molecules-16-02032" ref-type="bibr">68</xref>], it is presumed that resveratorol attenuate the activation of macrophages during influenza virus infection.</p><p>(+)-Vitisin A (<bold>17</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>), a tetramer of resveratrol, isolated from <italic>Vitis thunbergii</italic> was reported to have various bioactivities, including antioxidant, protection against platelet aggregation, to inhibit the biosynthesis of pro-inflammatory cytokine leukotriene B4, and to suppress TNF-α-induced monocyte chemoattractant protein production in primary human endothelial cells [<xref rid="B69-molecules-16-02032" ref-type="bibr">69</xref>,<xref rid="B70-molecules-16-02032" ref-type="bibr">70</xref>,<xref rid="B71-molecules-16-02032" ref-type="bibr">71</xref>]. Furthermore, (+)-vitisin A has been shown to inhibit the production of RANTES in airway epithelial cells after influenza A virus infection, the effect of which was much higher than that of resveratrol [<xref rid="B72-molecules-16-02032" ref-type="bibr">72</xref>]. Accordingly, it has been suggested that (+)-vitisin A may serve as a potential anti-inflammatory agent that interrupts the pathogenesis after viral infection.</p></sec><sec id="sec2dot3dot4-molecules-16-02032"><title>2.3.4. Ambroxol</title><p>Ambroxol (2-amino-3,5-dibromo-<italic>N</italic>-[trans-4-hydroxycyclohexyl]benzylamine, <bold>18</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>), known as a mucolytic agent, has been used for the treatment of chronic bronchitis and neonatal respiration distress syndrome [<xref rid="B73-molecules-16-02032" ref-type="bibr">73</xref>]. Ambroxol suppressed the proliferation of influenza virus in the mouse airway and improved the survival rate of mice [<xref rid="B74-molecules-16-02032" ref-type="bibr">74</xref>]. Antioxidant activity of ambroxol is related to the direct scavenging effect for ROS, such as superoxide anion and hydroxyl radicals [<xref rid="B75-molecules-16-02032" ref-type="bibr">75</xref>,<xref rid="B76-molecules-16-02032" ref-type="bibr">76</xref>]. Treatment with ambroxol also significantly decreased the incidence of acute upper respiratory diseases during winter season in humans [<xref rid="B77-molecules-16-02032" ref-type="bibr">77</xref>].</p></sec><sec id="sec2dot3dot5-molecules-16-02032"><title>2.3.5. Ascorbic acid</title><p>Ascorbic acid (<bold>19</bold>, <xref ref-type="fig" rid="molecules-16-02032-f004">Figure 4</xref>) scavenges superoxide anion [<xref rid="B78-molecules-16-02032" ref-type="bibr">78</xref>]. Ascorbic acid inhibited the proliferation of influenza virus in cell cultures [<xref rid="B79-molecules-16-02032" ref-type="bibr">79</xref>]. Dehydroascorbic acid, an oxidized form of ascorbic acid without reducing ability, showed much stronger antiviral activity than that of ascorbic acid, indicating that the antiviral activity of ascorbic acid is due to factors other than antioxidant mechanism [<xref rid="B80-molecules-16-02032" ref-type="bibr">80</xref>]. In a controlled trial of 226 patients with influenza A, 114 patients received vitamin C 300 mg/day, and 112 patients served as controls; outcomes measured were development of pneumonia and duration of hospital stay. Pneumonia was reported in two subjects in the treatment group and 10 in the control group, and hospital stays for influenza or related complications averaged nine days in the vitamin C group and 12 days in the control group [<xref rid="B81-molecules-16-02032" ref-type="bibr">81</xref>]. Therefore it has been considered that combined inhalation and oral supplementation of ascorbic acid may prevent influenza virus infection [<xref rid="B82-molecules-16-02032" ref-type="bibr">82</xref>].</p></sec></sec><sec id="sec2dot4-molecules-16-02032"><title>2.4. Flavonoids</title><p>Flavonoids are a ubiquitous group of polyphenolic substances which are present in most plants, concentrating in seeds, fruit skin or peel, bark, and flowers. The structural components common to these molecules include two benzene rings on either side of a 3-carbon ring. Multiple combinations of hydroxyl groups, sugars, oxygens, and methyl groups attached to these structures create the various classes of flavonoids: flavanols, flavanones, flavones, flavan-3-ols (catechins), anthocyanins, and isoflavones. Flavonoids have been shown in a number of studies to be potent antioxidants, capable of scavenging hydroxyl radicals, superoxide anions, and lipid peroxyl radicals [<xref rid="B83-molecules-16-02032" ref-type="bibr">83</xref>].</p><sec id="sec2dot4dot1-molecules-16-02032"><title>2.4.1. 5,7,4’-Trihydroxy-8-methoxyflavone</title><p>5,7,4’-Trihydroxy-8-methoxyflavone (F36, <bold>20</bold>, <xref ref-type="fig" rid="molecules-16-02032-f005">Figure 5</xref>) isolated from the roots of <italic>Scutellaria baicalensis</italic>, was shown to have a specific inhibitory activity against influenza virus NA because it did not affect the mouse liver NA activity [<xref rid="B84-molecules-16-02032" ref-type="bibr">84</xref>,<xref rid="B85-molecules-16-02032" ref-type="bibr">85</xref>]. F36 inhibited the proliferation of influenza virus in MDCK cells, in the allantoic sac of embryonal chicken egg and <italic>in vivo</italic> using BALB/c mice [<xref rid="B85-molecules-16-02032" ref-type="bibr">85</xref>,<xref rid="B86-molecules-16-02032" ref-type="bibr">86</xref>,<xref rid="B87-molecules-16-02032" ref-type="bibr">87</xref>]. Immunoelectron microscopic analysis revealed that F36 inhibited the budding of progeny influenza virus particles from MDCK cell surface and microvilli [<xref rid="B88-molecules-16-02032" ref-type="bibr">88</xref>].</p></sec><sec id="sec2dot4dot2-molecules-16-02032"><title>2.4.2. Catechins</title><p>Catechins from green tea: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin (EGC) (<bold>21</bold>, <bold>22</bold> and <bold>23</bold>, respectively, <xref ref-type="fig" rid="molecules-16-02032-f005">Figure 5</xref>) have been evaluated for their ability to inhibit influenza virus replication in cell culture [<xref rid="B89-molecules-16-02032" ref-type="bibr">89</xref>]. Among the test compounds, EGCG and ECG were found to be potent inhibitors of influenza virus replication in MDCK cell culture, and this effect was observed in all influenza virus subtypes tested, including A (H1N1), A (H3N2) and B virus. The 50% effective inhibition concentrations of EGCG, ECG, and EGC for influenza A virus were 22–28, 22–40 and 309–318 µM, respectively. EGCG and ECG exhibited inhibitory activity of hemagglutination, suppressed viral RNA synthesis in MDCK cells, and inhibited the NA activity, however, the effects of EGC were much lesser. The results show that the 3-galloyl group of catechin skeleton plays an important role on the observed antiviral activity, whereas the 5’-OH at the trihydroxybenzyl moiety at the 2-position plays a minor role. Catechins have been shown to possess the ability to scavenge for superoxide anion and hydroxyl radicals [<xref rid="B90-molecules-16-02032" ref-type="bibr">90</xref>]. Gargling with tea catechin extracts prevented influenza virus infection in elderly nursing home residents [<xref rid="B91-molecules-16-02032" ref-type="bibr">91</xref>]. Long chain monoester derivatives of EGCG enhanced the anti-influenza virus activity 24-fold relative to native EGCG [<xref rid="B92-molecules-16-02032" ref-type="bibr">92</xref>].</p><p>The influenza A RNA polymerase possesses endonuclease activity to digest the host mRNA. This endonuclease domain can be a target of anti-influenza A virus drug. Kizuhara and co-workers have reported that green tea catechins inhibited this viral endonuclease activity and that their galloyl group was important for their function [<xref rid="B93-molecules-16-02032" ref-type="bibr">93</xref>]. Docking simulations revealed that catechins with galloyl group fitted well into the active pocket of the endonuclease domain to enable stable binding. Their results provide useful data that make it possible to refine and optimize catechin-based drug design more readily for stability.</p></sec><sec id="sec2dot4dot3-molecules-16-02032"><title>2.4.3. Quercetin 3-rhamnoside</title><p>Quercetin 3-rhamnoside (Q3R, 24, <xref ref-type="fig" rid="molecules-16-02032-f005">Figure 5</xref>) from <italic>Houttuynia cordata</italic> possessed strong antiviral activity against influenza A/WS/33 virus as well as oseltamivir [<xref rid="B94-molecules-16-02032" ref-type="bibr">94</xref>]. Pre-exposure of the virus to Q3R did not alter the infectivity. When Q3R was added just after the virus infection or until four hours after the virus infection, the antiviral activity of Q3R was exhibited. Viral mRNA synthesis was inhibited by the treatment with Q3R. The mode of action of Q3R involved the inhibition of virus replication in the initial stage of virus infection by indirect interaction with virus particles.</p></sec><sec id="sec2dot4dot4-molecules-16-02032"><title>2.4.4. Isoquercetin</title><p>Isoquercetin (<bold>25</bold>, <xref ref-type="fig" rid="molecules-16-02032-f005">Figure 5</xref>) inhibited the replication of both influenza A and B viruses in cell cultures, the antiviral activity of which was much stronger than that of EGCG, resveratrol and quercetin [<xref rid="B95-molecules-16-02032" ref-type="bibr">95</xref>]. Combination of isoquercetin with amantadine synergistically reduced the viral replication <italic>in vitro</italic>. The serial passages of virus in the presence of isoquercetin did not lead to the emergence of resistant virus, and the addition of isoquercetin to amantadine or oseltamivir treatment suppressed the emergence of amantadine- or oseltamivir-resistant virus. In a mouse model of influenza virus infection, isoquercetin administered intraperitoneally to mice inoculated with human influenza A virus significantly decreased the virus titers and pathological changes in the lung. Therefore, it has been suggested that isoquercetin may have the potential to be developed as a therapeutic agent for the treatment of influenza virus infection and for the suppression of resistance in combination therapy with existing drugs.</p></sec><sec id="sec2dot4dot5-molecules-16-02032"><title>2.4.5. Oligonol</title><p>Oligonol was obtained by oligomerizing the polyphenol polymers found in lychee fruit pericarp [<xref rid="B96-molecules-16-02032" ref-type="bibr">96</xref>]. As indicated in <xref rid="molecules-16-02032-t001" ref-type="table">Table 1</xref>, oligonol contains 16.1% polyphenol monomers [(+)-catechin, (-)-epicatechin, ECG and EGCG] and 13.9% polyphenol dimer (procyanidin A1 <italic>etc.</italic>), while lychee fruit polyphenol contains 6.4% polyphenol monomer and 9.9% polyphenol dimer [<xref rid="B97-molecules-16-02032" ref-type="bibr">97</xref>]. </p><p>Oligonol was approved as a New Dietary Ingredient by the United States Food and Drug Administration in 2007, and is commercially available at present (Amino Up Chemical Co., Ltd., Sapporo, Japan). Oligonol inhibits influenza virus proliferation by blocking attachment of the virus to MDCK cells and by suppression of nuclear export of influenza virus ribonucleoprotein (RNP) [<xref rid="B97-molecules-16-02032" ref-type="bibr">97</xref>]. Influenza virus infection induced the production of ROS and the phosphorylation of extracellular-signal-regulated kinase (ERK) in MDCK cells. Inhibition of ERK activation by a dominant negative mutant of ERK or NAC led to the suppression of viral RNP nuclear export. Phorbol 12-myristate 13-acetate (PMA) induced ROS production, ERK phosphorylation and enhanced influenza proliferation in MDCK cells. Oligonol and NAC inhibit PMA-induced ERK phosphorylation and ROS production. These results suggest that the inhibitory effect of oligonol on influenza virus RNP nuclear export is implicated in the blocking of ROS-dependent induction of ERK phosphorylation.</p></sec></sec></sec><sec id="sec3-molecules-16-02032"><title>3. Conclusions</title><p>Scavenging of superoxide is an important tool in the development of new strategies for the prevention of organ failure during severe influenza-associated complications. Since the most important aspect in viral disease treatment is to inhibit virus replication, an agent with antiviral and antioxidant activities should be a drug of choice for the treatment of patients with severe influenza-associated complications. Selected compounds, such as PDTC, NAC, glutathione, NDGA, thujaplicin, resveratrol, (+)-vitisin A, ambroxol, ascorbic acid, F36, EGCG, ECG, Q3R, isoquercetin and oligonol, possess both antiviral and antioxidant activities. Consequently, they are potential drugs of interest for severe influenza-associated complications. In theory, combination of these antioxidants with current anti-influenza drugs could improve conventional chemotherapy for severe influenza-associated complications.</p></sec></body><back><ack><title>Acknowledgements</title><p>This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology, by the Promotion and Mutual Aid Corporation for Private School of Japan, and by the TUPLUS innovative Research Promotion Grant from Tokyo University of Pharmacy and Life Sciences.</p></ack><fn-group><fn><p><italic>Sample Availability:</italic> Samples of the compounds <bold>8</bold>, <bold>9</bold> and <bold>10</bold> are available from the authors.</p></fn></fn-group><ref-list><title>References</title><ref id="B1-molecules-16-02032"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Peiris</surname><given-names>J.S.</given-names></name><name><surname>Tu</surname><given-names>W.W.</given-names></name><name><surname>Yen</surname><given-names>H.L.</given-names></name></person-group><article-title>A novel H1N1 virus causes the first pandemic of the 21<sup>st</sup> century</article-title><source>Eur. J. Immunol.</source><year>2009</year><volume>39</volume><fpage>2946</fpage><lpage>2954</lpage><pub-id pub-id-type="doi">10.1002/eji.200939911</pub-id><pub-id pub-id-type="pmid">19790188</pub-id></element-citation></ref><ref id="B2-molecules-16-02032"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chang</surname><given-names>L.Y.</given-names></name><name><surname>Shih</surname><given-names>S.R.</given-names></name><name><surname>Shao</surname><given-names>P.L.</given-names></name><name><surname>Huang</surname><given-names>D.T.</given-names></name><name><surname>Huang</surname><given-names>L.M.</given-names></name></person-group><article-title>Novel swine-origin influenza virus A (H1N1): The first pandemic of the 21<sup>st</sup> century</article-title><source>J. Formos. Med. Assoc.</source><year>2009</year><volume>108</volume><fpage>526</fpage><lpage>532</lpage><pub-id pub-id-type="doi">10.1016/S0929-6646(09)60369-7</pub-id><pub-id pub-id-type="pmid">19586825</pub-id></element-citation></ref><ref id="B3-molecules-16-02032"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rothberg</surname><given-names>M.B.</given-names></name><name><surname>Haessler</surname><given-names>S.D.</given-names></name></person-group><article-title>Complications of seasonal and pandemic influenza</article-title><source>Crit. Care Med.</source><year>2010</year><volume>38</volume><fpage>e91</fpage><lpage>e97</lpage><pub-id pub-id-type="doi">10.1097/CCM.0b013e3181c92eeb</pub-id><pub-id pub-id-type="pmid">19935413</pub-id></element-citation></ref><ref id="B4-molecules-16-02032"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Girard</surname><given-names>M.P.</given-names></name><name><surname>Tam</surname><given-names>J.S.</given-names></name><name><surname>Assossou</surname><given-names>O.M.</given-names></name><name><surname>Kieny</surname><given-names>M.P.</given-names></name></person-group><article-title>The 2009 A (H1N1) influenza virus pandemic: A review</article-title><source>Vaccine</source><year>2010</year><volume>28</volume><fpage>4895</fpage><lpage>4902</lpage><pub-id pub-id-type="doi">10.1016/j.vaccine.2010.05.031</pub-id><pub-id pub-id-type="pmid">20553769</pub-id></element-citation></ref><ref id="B5-molecules-16-02032"><label>5.</label><element-citation publication-type="web"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group><source>Pandemic (H1N1) 2009 - update 111</source><comment>Available online: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/2010_07_30/en/index.html">http://www.who.int/csr/ don/2010_07_30/en/index.html</ext-link></comment><date-in-citation content-type="access-date" iso-8601-date="2011-02-26">(Accessed on 26 February 2011)</date-in-citation></element-citation></ref><ref id="B6-molecules-16-02032"><label>6.</label><element-citation publication-type="web"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group><source>Influenza updates</source><comment>Available online: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/2010_09_10/en/index.html">http://www.who.int/csr/don/2010_09_10/ en/index.html</ext-link></comment><date-in-citation content-type="access-date" iso-8601-date="2011-02-26">(Accessed on 26 February 2011)</date-in-citation></element-citation></ref><ref id="B7-molecules-16-02032"><label>7.</label><element-citation publication-type="book"><person-group person-group-type="author"><name><surname>Kamps</surname><given-names>B.S.</given-names></name><name><surname>Reyes-Terán</surname><given-names>G.</given-names></name></person-group><article-title>Influenza</article-title><source>Influenza Report</source><person-group person-group-type="editor"><name><surname>Kamps</surname><given-names>B.S.</given-names></name><name><surname>Hoffmann</surname><given-names>C.</given-names></name><name><surname>Preiser</surname><given-names>W.</given-names></name></person-group><publisher-name>Flying Publishers</publisher-name><publisher-loc>Paris, France</publisher-loc><year>2006</year><fpage>17</fpage><lpage>47</lpage></element-citation></ref><ref id="B8-molecules-16-02032"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Beigel</surname><given-names>J.</given-names></name><name><surname>Bray</surname><given-names>M.</given-names></name></person-group><article-title>Current and future antiviral therapy of severe seasonal and avian influenza</article-title><source>Antivir. Res.</source><year>2008</year><volume>78</volume><fpage>91</fpage><lpage>102</lpage><pub-id pub-id-type="doi">10.1016/j.antiviral.2008.01.003</pub-id><pub-id pub-id-type="pmid">18328578</pub-id></element-citation></ref><ref id="B9-molecules-16-02032"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>Centers for Disease Control and Prevention (CDC)</collab></person-group><article-title>Update: Drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009</article-title><source>MMWR Morb. Mortal. Wkly. Rep.</source><year>2009</year><volume>58</volume><fpage>433</fpage><lpage>435</lpage><pub-id pub-id-type="pmid">19407738</pub-id></element-citation></ref><ref id="B10-molecules-16-02032"><label>10.</label><element-citation publication-type="web"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group><source>Pandemic (H1N1) 2009 - update 60</source><comment>Available online: <ext-link ext-link-type="uri" xlink:href="http://www.who.int/csr/don/2009_08_04/en/index.html">http://www.who.int/csr/ don/2009_08_04/en/index.html</ext-link></comment><date-in-citation content-type="access-date" iso-8601-date="2011-02-26">(Accessed on 26 February 2011)</date-in-citation></element-citation></ref><ref id="B11-molecules-16-02032"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><collab>World Health Organization</collab></person-group><article-title>Update on oseltamivir-resistant pandemic A (H1N1) 2009 influenza virus: January 2010</article-title><source>Wkly. Epidemiol. Rec.</source><year>2010</year><volume>85</volume><fpage>37</fpage><lpage>40</lpage></element-citation></ref><ref id="B12-molecules-16-02032"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sugaya</surname><given-names>N.</given-names></name><name><surname>Ohashi</surname><given-names>Y.</given-names></name></person-group><article-title>Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) <italic>versus</italic> oseltamivir as treatment for children with influenza virus infection</article-title><source>Antimicrob. Agents Chemother.</source><year>2010</year><volume>54</volume><fpage>2575</fpage><lpage>2582</lpage><pub-id pub-id-type="doi">10.1128/AAC.01755-09</pub-id><pub-id pub-id-type="pmid">20368393</pub-id></element-citation></ref><ref id="B13-molecules-16-02032"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bearman</surname><given-names>G.M.</given-names></name><name><surname>Shankaran</surname><given-names>S.</given-names></name><name><surname>Elam</surname><given-names>K.</given-names></name></person-group><article-title>Treatment of severe cases of pandemic (H1N1) 2009 influenza: Review of antivirals and adjuvant therapy</article-title><source>Recent Patents Antiinfect. Drug Discov.</source><year>2010</year><volume>5</volume><fpage>152</fpage><lpage>156</lpage></element-citation></ref><ref id="B14-molecules-16-02032"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nasu</surname><given-names>T.</given-names></name><name><surname>Ogawa</surname><given-names>D.</given-names></name><name><surname>Wada</surname><given-names>J.</given-names></name><name><surname>Makino</surname><given-names>H.</given-names></name></person-group><article-title>Peramivir for severe influenza infection in a patient with diabetic nephropathy</article-title><source>Am. J. Respir. Crit. Care Med.</source><year>2010</year><volume>182</volume><fpage>1209</fpage><lpage>1210</lpage><pub-id pub-id-type="doi">10.1164/ajrccm.182.9.1209</pub-id><pub-id pub-id-type="pmid">21041567</pub-id></element-citation></ref><ref id="B15-molecules-16-02032"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Renaud</surname><given-names>C.</given-names></name><name><surname>Pergam</surname><given-names>S.A.</given-names></name><name><surname>Polyak</surname><given-names>C.</given-names></name><name><surname>Jain</surname><given-names>R.</given-names></name><name><surname>Kuypers</surname><given-names>J.</given-names></name><name><surname>Englund</surname><given-names>J.A.</given-names></name><name><surname>Corey</surname><given-names>L.</given-names></name><name><surname>Boeckh</surname><given-names>M.J.</given-names></name></person-group><article-title>Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir</article-title><source>Transpl. Infect. Dis.</source><year>2010</year><volume>12</volume><fpage>513</fpage><lpage>517</lpage><pub-id pub-id-type="doi">10.1111/j.1399-3062.2010.00582.x</pub-id><pub-id pub-id-type="pmid">21062390</pub-id></element-citation></ref><ref id="B16-molecules-16-02032"><label>16.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cunha</surname><given-names>B.A.</given-names></name><name><surname>Syed</surname><given-names>U.</given-names></name><name><surname>Mickail</surname><given-names>N.</given-names></name></person-group><article-title>Fulminant fatal swine influenza (H1N1): Myocarditis, myocardial infarction, or severe influenza pneumonia?</article-title><source>Heart Lung</source><year>2010</year><volume>39</volume><fpage>453</fpage><lpage>458</lpage><pub-id pub-id-type="doi">10.1016/j.hrtlng.2010.04.003</pub-id><pub-id pub-id-type="pmid">20831976</pub-id></element-citation></ref><ref id="B17-molecules-16-02032"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nguyen</surname><given-names>J.T.</given-names></name><name><surname>Hoopes</surname><given-names>J.D.</given-names></name><name><surname>Le</surname><given-names>M.H.</given-names></name><name><surname>Smee</surname><given-names>D.F.</given-names></name><name><surname>Patick</surname><given-names>A.K.</given-names></name><name><surname>Faix</surname><given-names>D.J.</given-names></name><name><surname>Blair</surname><given-names>P.J.</given-names></name><name><surname>de Jong</surname><given-names>M.D.</given-names></name><name><surname>Prichard</surname><given-names>M.N.</given-names></name><name><surname>Went</surname><given-names>G.T.</given-names></name></person-group><article-title>Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains <italic>in vitro</italic></article-title><source>PLoS One</source><year>2010</year><volume>5</volume><elocation-id>e9332</elocation-id><pub-id pub-id-type="doi">10.1371/journal.pone.0009332</pub-id><pub-id pub-id-type="pmid">20179772</pub-id></element-citation></ref><ref id="B18-molecules-16-02032"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tumpey</surname><given-names>T.M.</given-names></name><name><surname>García-Sastre</surname><given-names>A.</given-names></name><name><surname>Taubenberger</surname><given-names>J.K.</given-names></name><name><surname>Palese</surname><given-names>P.</given-names></name><name><surname>Swayne</surname><given-names>D.E.</given-names></name><name><surname>Pantin-Jackwood</surname><given-names>M.J.</given-names></name><name><surname>Schultz-Cherry</surname><given-names>S.</given-names></name><name><surname>Solórzano</surname><given-names>A.</given-names></name><name><surname>Van Rooijen</surname><given-names>N.</given-names></name><name><surname>Katz</surname><given-names>J.M.</given-names></name><name><surname>Basler</surname><given-names>C.F.</given-names></name></person-group><article-title>Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: Functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice</article-title><source>J. Virol.</source><year>2005</year><volume>79</volume><fpage>14933</fpage><lpage>14944</lpage><pub-id pub-id-type="doi">10.1128/JVI.79.23.14933-14944.2005</pub-id><pub-id pub-id-type="pmid">16282492</pub-id></element-citation></ref><ref id="B19-molecules-16-02032"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Toyoda</surname><given-names>H.</given-names></name></person-group><article-title>Current status of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection</article-title><source>Gene Regul. Syst. Biol.</source><year>2007</year><volume>1</volume><fpage>295</fpage><lpage>302</lpage><pub-id pub-id-type="doi">10.4137/GRSB.S374</pub-id></element-citation></ref><ref id="B20-molecules-16-02032"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akaike</surname><given-names>T.</given-names></name><name><surname>Suga</surname><given-names>M.</given-names></name><name><surname>Maeda</surname><given-names>H.</given-names></name></person-group><article-title>Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO</article-title><source>Proc. Soc. Exp. Biol. Med.</source><year>1998</year><volume>217</volume><fpage>64</fpage><lpage>73</lpage><pub-id pub-id-type="doi">10.3181/00379727-217-44206</pub-id><pub-id pub-id-type="pmid">9421208</pub-id></element-citation></ref><ref id="B21-molecules-16-02032"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Toyoda</surname><given-names>H.</given-names></name></person-group><article-title>Potential of selected antioxidants for influenza chemotherapy</article-title><source>Anti-Infect. Agents Med. Chem.</source><year>2008</year><volume>7</volume><fpage>73</fpage><lpage>83</lpage><pub-id pub-id-type="doi">10.2174/187152108783954605</pub-id></element-citation></ref><ref id="B22-molecules-16-02032"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Toyoda</surname><given-names>H.</given-names></name></person-group><article-title>Future target molecules for influenza treatment</article-title><source>Mini-Rev. Med. Chem.</source><year>2008</year><volume>8</volume><fpage>491</fpage><lpage>495</lpage><pub-id pub-id-type="doi">10.2174/138955708784223530</pub-id><pub-id pub-id-type="pmid">18473937</pub-id></element-citation></ref><ref id="B23-molecules-16-02032"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oda</surname><given-names>T.</given-names></name><name><surname>Akaike</surname><given-names>T.</given-names></name><name><surname>Hamamoto</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>F.</given-names></name><name><surname>Hirano</surname><given-names>T.</given-names></name><name><surname>Maeda</surname><given-names>H.</given-names></name></person-group><article-title>Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD</article-title><source>Science</source><year>1989</year><volume>244</volume><fpage>974</fpage><lpage>976</lpage><pub-id pub-id-type="doi">10.1126/science.2543070</pub-id><pub-id pub-id-type="pmid">2543070</pub-id></element-citation></ref><ref id="B24-molecules-16-02032"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sidwell</surname><given-names>R.W.</given-names></name><name><surname>Huffman</surname><given-names>J.H.</given-names></name><name><surname>Bailey</surname><given-names>K.W.</given-names></name><name><surname>Wong</surname><given-names>M.H.</given-names></name><name><surname>Nimrod</surname><given-names>A.</given-names></name><name><surname>Panet</surname><given-names>A.</given-names></name></person-group><article-title>Inhibitory effects of recombinant manganese superoxide dismutase on influenza virus infections in mice</article-title><source>Antimicrob. Agents Chemother.</source><year>1996</year><volume>40</volume><fpage>2626</fpage><lpage>2631</lpage><pub-id pub-id-type="pmid">8913477</pub-id></element-citation></ref><ref id="B25-molecules-16-02032"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Serkedjieva</surname><given-names>J.</given-names></name><name><surname>Roeva</surname><given-names>I.</given-names></name><name><surname>Angelova</surname><given-names>M.</given-names></name><name><surname>Dolashka</surname><given-names>P.</given-names></name><name><surname>Voelter</surname><given-names>W.G.</given-names></name></person-group><article-title>Combined protective effect of a fungal Cu/Zn-containing superoxide dismutase and rimantadine hydrochloride in experimental murine influenza a virus infection</article-title><source>Acta Virol.</source><year>2003</year><volume>47</volume><fpage>53</fpage><lpage>56</lpage><pub-id pub-id-type="pmid">12828346</pub-id></element-citation></ref><ref id="B26-molecules-16-02032"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akaike</surname><given-names>T.</given-names></name><name><surname>Ando</surname><given-names>M.</given-names></name><name><surname>Oda</surname><given-names>T.</given-names></name><name><surname>Doi</surname><given-names>T.</given-names></name><name><surname>Ijiri</surname><given-names>S.</given-names></name><name><surname>Araki</surname><given-names>S.</given-names></name><name><surname>Maeda</surname><given-names>H.</given-names></name></person-group><article-title>Dependence on O<sub>2</sub><sup>-</sup> generation by xanthine oxidase of pathogenesis of influenza virus infection in mice</article-title><source>J. Clin. Invest.</source><year>1990</year><volume>85</volume><fpage>739</fpage><lpage>745</lpage><pub-id pub-id-type="doi">10.1172/JCI114499</pub-id><pub-id pub-id-type="pmid">2155924</pub-id></element-citation></ref><ref id="B27-molecules-16-02032"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Suliman</surname><given-names>H.B.</given-names></name><name><surname>Ryan</surname><given-names>L.K.</given-names></name><name><surname>Bishop</surname><given-names>L.</given-names></name><name><surname>Folz</surname><given-names>R.J.</given-names></name></person-group><article-title>Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase</article-title><source>Am. J. Physiol. Lung Cell Mol. Physiol.</source><year>2001</year><volume>280</volume><fpage>L69</fpage><lpage>L78</lpage><pub-id pub-id-type="doi">10.1152/ajplung.2001.280.1.L69</pub-id><pub-id pub-id-type="pmid">11133496</pub-id></element-citation></ref><ref id="B28-molecules-16-02032"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Snelgrove</surname><given-names>R.J.</given-names></name><name><surname>Edwards</surname><given-names>L.</given-names></name><name><surname>Rae</surname><given-names>A.J.</given-names></name><name><surname>Hussell</surname><given-names>T.</given-names></name></person-group><article-title>An absence of reactive oxygen species improves the resolution of lung influenza infection</article-title><source>Eur. J. Immunol.</source><year>2006</year><volume>36</volume><fpage>1364</fpage><lpage>1373</lpage><pub-id pub-id-type="doi">10.1002/eji.200635977</pub-id><pub-id pub-id-type="pmid">16703568</pub-id></element-citation></ref><ref id="B29-molecules-16-02032"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shi</surname><given-names>Y.</given-names></name><name><surname>Niculescu</surname><given-names>R.</given-names></name><name><surname>Wang</surname><given-names>D.</given-names></name><name><surname>Patel</surname><given-names>S.</given-names></name><name><surname>Davenpeck</surname><given-names>K.L.</given-names></name><name><surname>Zalewski</surname><given-names>A.</given-names></name></person-group><article-title>Increased NAD(P)H oxidase and reactive oxygen species in coronary arteries after balloon injury</article-title><source>Arterioscler. Thromb. Vasc. Biol.</source><year>2001</year><volume>21</volume><fpage>739</fpage><lpage>745</lpage><pub-id pub-id-type="doi">10.1161/01.ATV.21.5.739</pub-id><pub-id pub-id-type="pmid">11348868</pub-id></element-citation></ref><ref id="B30-molecules-16-02032"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Ohyama</surname><given-names>K.</given-names></name></person-group><article-title>Antiviral function of pyrrolidine dithiocarbamate against influenza virus: The inhibition of viral gene replication and transcription</article-title><source>J. Antimicrob. Chemother.</source><year>2003</year><volume>52</volume><fpage>8</fpage><lpage>10</lpage><pub-id pub-id-type="doi">10.1093/jac/dkg282</pub-id><pub-id pub-id-type="pmid">12775674</pub-id></element-citation></ref><ref id="B31-molecules-16-02032"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Ohyama</surname><given-names>K.</given-names></name><name><surname>Bessho</surname><given-names>T.</given-names></name><name><surname>Yuan</surname><given-names>B.</given-names></name><name><surname>Yamakawa</surname><given-names>T.</given-names></name></person-group><article-title>Effect of antioxidants on apoptosis induced by influenza virus infection: Inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate</article-title><source>Antivir. Res.</source><year>2002</year><volume>56</volume><fpage>207</fpage><lpage>217</lpage><pub-id pub-id-type="doi">10.1016/S0166-3542(02)00109-2</pub-id><pub-id pub-id-type="pmid">12406505</pub-id></element-citation></ref><ref id="B32-molecules-16-02032"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Knobil</surname><given-names>K.</given-names></name><name><surname>Choi</surname><given-names>A.M.</given-names></name><name><surname>Weigand</surname><given-names>G.W.</given-names></name><name><surname>Jacoby</surname><given-names>D.B.</given-names></name></person-group><article-title>Role of oxidants in influenza virus-induced gene expression</article-title><source>Am. J. Physiol.</source><year>1998</year><volume>274</volume><fpage>L134</fpage><lpage>L142</lpage><pub-id pub-id-type="doi">10.1152/ajplung.1998.274.1.L134</pub-id><pub-id pub-id-type="pmid">9458811</pub-id></element-citation></ref><ref id="B33-molecules-16-02032"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lowy</surname><given-names>R.J.</given-names></name><name><surname>Dimitrov</surname><given-names>D.S.</given-names></name></person-group><article-title>Characterization of influenza virus-induced death of J774.1 macrophages</article-title><source>Exp. Cell Res.</source><year>1997</year><volume>234</volume><fpage>249</fpage><lpage>258</lpage><pub-id pub-id-type="doi">10.1006/excr.1997.3602</pub-id><pub-id pub-id-type="pmid">9260892</pub-id></element-citation></ref><ref id="B34-molecules-16-02032"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McKinney</surname><given-names>L.C.</given-names></name><name><surname>Galliger</surname><given-names>S.J.</given-names></name><name><surname>Lowy</surname><given-names>R.J.</given-names></name></person-group><article-title>Active and inactive influenza virus induction of tumor necrosis factor-α and nitric oxide in J774.1 murine macrophages: Modulation by interferon-γ and failure to induce apoptosis</article-title><source>Virus Res.</source><year>2003</year><volume>97</volume><fpage>117</fpage><lpage>126</lpage><pub-id pub-id-type="doi">10.1016/j.virusres.2003.08.007</pub-id><pub-id pub-id-type="pmid">14602203</pub-id></element-citation></ref><ref id="B35-molecules-16-02032"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>K.</given-names></name><name><surname>Long</surname><given-names>Y.M.</given-names></name><name><surname>Wang</surname><given-names>H.</given-names></name><name><surname>Lan</surname><given-names>L.</given-names></name><name><surname>Lin</surname><given-names>Z.H.</given-names></name></person-group><article-title>Activation of nuclear factor-κB and effects of pyrrolidine dithiocarbamate on TNBS-induced rat colitis</article-title><source>World J. Gastroenterol.</source><year>2005</year><volume>11</volume><fpage>1508</fpage><lpage>1514</lpage><pub-id pub-id-type="doi">10.3748/wjg.v11.i10.1508</pub-id><pub-id pub-id-type="pmid">15770728</pub-id></element-citation></ref><ref id="B36-molecules-16-02032"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cuzzocrea</surname><given-names>S.</given-names></name><name><surname>Chatterjee</surname><given-names>P.K.</given-names></name><name><surname>Mazzon</surname><given-names>E.</given-names></name><name><surname>Dugo</surname><given-names>L.</given-names></name><name><surname>Serraino</surname><given-names>I.</given-names></name><name><surname>Britti</surname><given-names>D.</given-names></name><name><surname>Mazzullo</surname><given-names>G.</given-names></name><name><surname>Caputi</surname><given-names>A.P.</given-names></name><name><surname>Thiemermann</surname><given-names>C.</given-names></name></person-group><article-title>Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation</article-title><source>Br. J. Pharmacol.</source><year>2002</year><volume>135</volume><fpage>496</fpage><lpage>510</lpage><pub-id pub-id-type="doi">10.1038/sj.bjp.0704463</pub-id><pub-id pub-id-type="pmid">11815386</pub-id></element-citation></ref><ref id="B37-molecules-16-02032"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mallick</surname><given-names>I.H.</given-names></name><name><surname>Yang</surname><given-names>W.X.</given-names></name><name><surname>Winslet</surname><given-names>M.C.</given-names></name><name><surname>Seifalian</surname><given-names>A.M.</given-names></name></person-group><article-title>Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine</article-title><source>World J. Gastroenterol.</source><year>2005</year><volume>11</volume><fpage>7308</fpage><lpage>7313</lpage><pub-id pub-id-type="doi">10.3748/wjg.v11.i46.7308</pub-id><pub-id pub-id-type="pmid">16437633</pub-id></element-citation></ref><ref id="B38-molecules-16-02032"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>C.H.</given-names></name><name><surname>Fang</surname><given-names>I.M.</given-names></name><name><surname>Lin</surname><given-names>C.P.</given-names></name><name><surname>Yang</surname><given-names>C.M.</given-names></name><name><surname>Chen</surname><given-names>M.S.</given-names></name></person-group><article-title>Effects of the NF-κB inhibitor pyrrolidine dithiocarbamate on experimentally induced autoimmune anterior uveitis</article-title><source>Invest. Ophthalmol. Vis. Sci.</source><year>2005</year><volume>46</volume><fpage>1339</fpage><lpage>1347</lpage><pub-id pub-id-type="doi">10.1167/iovs.04-0640</pub-id><pub-id pub-id-type="pmid">15790900</pub-id></element-citation></ref><ref id="B39-molecules-16-02032"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>C.H.</given-names></name><name><surname>Kim</surname><given-names>J.H.</given-names></name><name><surname>Hsu</surname><given-names>C.Y.</given-names></name><name><surname>Ahn</surname><given-names>Y.S.</given-names></name></person-group><article-title>Zinc is required in pyrrolidine dithiocarbamate inhibition of NF-κB activation</article-title><source>FEBS Lett.</source><year>1999</year><volume>449</volume><fpage>28</fpage><lpage>32</lpage><pub-id pub-id-type="doi">10.1016/S0014-5793(99)00390-7</pub-id><pub-id pub-id-type="pmid">10225421</pub-id></element-citation></ref><ref id="B40-molecules-16-02032"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Oxford</surname><given-names>J.S.</given-names></name><name><surname>Perrin</surname><given-names>D.D.</given-names></name></person-group><article-title>Inhibition of the particle-associated RNA-dependent RNA polymerase activity of influenza viruses by chelating agents</article-title><source>J. Gen. Virol.</source><year>1974</year><volume>23</volume><fpage>59</fpage><lpage>71</lpage><pub-id pub-id-type="doi">10.1099/0022-1317-23-1-59</pub-id><pub-id pub-id-type="pmid">4833601</pub-id></element-citation></ref><ref id="B41-molecules-16-02032"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Si</surname><given-names>X.</given-names></name><name><surname>McManus</surname><given-names>B.M.</given-names></name><name><surname>Zhang</surname><given-names>J.</given-names></name><name><surname>Yuan</surname><given-names>J.</given-names></name><name><surname>Cheung</surname><given-names>C.</given-names></name><name><surname>Esfandiarei</surname><given-names>M.</given-names></name><name><surname>Suarez</surname><given-names>A.</given-names></name><name><surname>Morgan</surname><given-names>A.</given-names></name><name><surname>Luo</surname><given-names>H.</given-names></name></person-group><article-title>Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through inhibition of the ubiquitin-proteasome pathway</article-title><source>J. Virol.</source><year>2005</year><volume>79</volume><fpage>8014</fpage><lpage>8023</lpage><pub-id pub-id-type="doi">10.1128/JVI.79.13.8014-8023.2005</pub-id><pub-id pub-id-type="pmid">15956547</pub-id></element-citation></ref><ref id="B42-molecules-16-02032"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Krenn</surname><given-names>B.M.</given-names></name><name><surname>Holzer</surname><given-names>B.</given-names></name><name><surname>Gaudernak</surname><given-names>E.</given-names></name><name><surname>Triendl</surname><given-names>A.</given-names></name><name><surname>van Kuppeveld</surname><given-names>F.J.</given-names></name><name><surname>Seipelt</surname><given-names>J.</given-names></name></person-group><article-title>Inhibition of polyprotein processing and RNA replication of human rhinovirus by pyrrolidine dithiocarbamate involves metal ions</article-title><source>J. Virol.</source><year>2005</year><volume>79</volume><fpage>13892</fpage><lpage>13899</lpage><pub-id pub-id-type="doi">10.1128/JVI.79.22.13892-13899.2005</pub-id><pub-id pub-id-type="pmid">16254325</pub-id></element-citation></ref><ref id="B43-molecules-16-02032"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Ohyama</surname><given-names>K.</given-names></name><name><surname>Bessho</surname><given-names>T.</given-names></name><name><surname>Toyoda</surname><given-names>H.</given-names></name></person-group><article-title>Effects of mitogen-activated protein kinase inhibitors on tumor necrosis factor-α gene expression and apoptosis induction in cultured human fetal membrane chorion cells infected with influenza virus</article-title><source>Intervirology</source><year>2007</year><volume>50</volume><fpage>99</fpage><lpage>107</lpage><pub-id pub-id-type="doi">10.1159/000097396</pub-id><pub-id pub-id-type="pmid">17139186</pub-id></element-citation></ref><ref id="B44-molecules-16-02032"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chiou</surname><given-names>W.F.</given-names></name><name><surname>Chen</surname><given-names>C.C.</given-names></name><name><surname>Wei</surname><given-names>B.L.</given-names></name></person-group><article-title>8-Prenylkaempferol suppresses influenza A virus-induced RANTES production in A549 cells via blocking PI3K-mediated transcriptional activation of NF-κB and IRF3</article-title><source>Evid. Based Complement. Altern. Med.</source><year>2009</year><comment>In Press</comment><pub-id pub-id-type="doi">10.1093/ecam/nep066</pub-id><pub-id pub-id-type="pmid">19592477</pub-id></element-citation></ref><ref id="B45-molecules-16-02032"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kelly</surname><given-names>G.S.</given-names></name></person-group><article-title>Clinical applications of <italic>N</italic>-acetylcysteine</article-title><source>Altern. Med. Rev.</source><year>1998</year><volume>3</volume><fpage>114</fpage><lpage>127</lpage><pub-id pub-id-type="pmid">9577247</pub-id></element-citation></ref><ref id="B46-molecules-16-02032"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saito</surname><given-names>T.</given-names></name><name><surname>Tanaka</surname><given-names>M.</given-names></name><name><surname>Yamaguchi</surname><given-names>I.</given-names></name></person-group><article-title>Effect of brefeldin A on influenza A virus-induced apoptosis <italic>in vitro</italic></article-title><source>J. Vet. Med. Sci.</source><year>1996</year><volume>58</volume><fpage>1137</fpage><lpage>1139</lpage><pub-id pub-id-type="doi">10.1292/jvms.58.11_1137</pub-id><pub-id pub-id-type="pmid">8959666</pub-id></element-citation></ref><ref id="B47-molecules-16-02032"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>C.</given-names></name><name><surname>Zimmer</surname><given-names>S.G.</given-names></name><name><surname>Lu</surname><given-names>Z.</given-names></name><name><surname>Holland</surname><given-names>R.E.</given-names><suffix>Jr.</suffix></name><name><surname>Dong</surname><given-names>Q.</given-names></name><name><surname>Chambers</surname><given-names>T.M.</given-names></name></person-group><article-title>The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis</article-title><source>Virology</source><year>2001</year><volume>287</volume><fpage>202</fpage><lpage>213</lpage><pub-id pub-id-type="doi">10.1006/viro.2001.1010</pub-id><pub-id pub-id-type="pmid">11504555</pub-id></element-citation></ref><ref id="B48-molecules-16-02032"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geiler</surname><given-names>J.</given-names></name><name><surname>Michaelis</surname><given-names>M.</given-names></name><name><surname>Naczk</surname><given-names>P.</given-names></name><name><surname>Leutz</surname><given-names>A.</given-names></name><name><surname>Langer</surname><given-names>K.</given-names></name><name><surname>Doerr</surname><given-names>H.W.</given-names></name><name><surname>Cinatl</surname><given-names>J.</given-names><suffix>Jr.</suffix></name></person-group><article-title><italic>N</italic>-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus</article-title><source>Biochem. Pharmacol.</source><year>2009</year><volume>79</volume><fpage>413</fpage><lpage>420</lpage><pub-id pub-id-type="doi">10.1016/j.bcp.2009.08.025</pub-id><pub-id pub-id-type="pmid">19732754</pub-id></element-citation></ref><ref id="B49-molecules-16-02032"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ungheri</surname><given-names>D.</given-names></name><name><surname>Pisani</surname><given-names>C.</given-names></name><name><surname>Sanson</surname><given-names>G.</given-names></name><name><surname>Bertani</surname><given-names>A.</given-names></name><name><surname>Schioppacassi</surname><given-names>G.</given-names></name><name><surname>Delgado</surname><given-names>R.</given-names></name><name><surname>Sironi</surname><given-names>M.</given-names></name><name><surname>Ghezzi</surname><given-names>P.</given-names></name></person-group><article-title>Protective effect of <italic>N</italic>-acetylcysteine in a model of influenza infection in mice</article-title><source>Int. J. Immunopathol. Pharmacol.</source><year>2000</year><volume>13</volume><fpage>123</fpage><lpage>128</lpage><pub-id pub-id-type="pmid">12657201</pub-id></element-citation></ref><ref id="B50-molecules-16-02032"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ghezzi</surname><given-names>P.</given-names></name><name><surname>Ungheri</surname><given-names>D.</given-names></name></person-group><article-title>Synergistic combination of <italic>N</italic>-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model</article-title><source>Int. J. Immunopathol. Pharmacol.</source><year>2004</year><volume>17</volume><fpage>99</fpage><lpage>102</lpage><pub-id pub-id-type="doi">10.1177/039463200401700114</pub-id><pub-id pub-id-type="pmid">15000873</pub-id></element-citation></ref><ref id="B51-molecules-16-02032"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Garozzo</surname><given-names>A.</given-names></name><name><surname>Tempera</surname><given-names>G.</given-names></name><name><surname>Ungheri</surname><given-names>D.</given-names></name><name><surname>Timpanaro</surname><given-names>R.</given-names></name><name><surname>Castro</surname><given-names>A.</given-names></name></person-group><article-title><italic>N</italic>-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection</article-title><source>Int. J. Immunopathol. Pharmacol.</source><year>2007</year><volume>20</volume><fpage>349</fpage><lpage>354</lpage><pub-id pub-id-type="doi">10.1177/039463200702000215</pub-id><pub-id pub-id-type="pmid">17624247</pub-id></element-citation></ref><ref id="B52-molecules-16-02032"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>De Flora</surname><given-names>S.</given-names></name><name><surname>Grassi</surname><given-names>C.</given-names></name><name><surname>Carati</surname><given-names>L.</given-names></name></person-group><article-title>Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term <italic>N</italic>-acetylcysteine treatment</article-title><source>Eur. Respir. J.</source><year>1997</year><volume>10</volume><fpage>1535</fpage><lpage>1541</lpage><pub-id pub-id-type="doi">10.1183/09031936.97.10071535</pub-id><pub-id pub-id-type="pmid">9230243</pub-id></element-citation></ref><ref id="B53-molecules-16-02032"><label>53.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lai</surname><given-names>K.Y.</given-names></name><name><surname>Ng</surname><given-names>W.Y.</given-names></name><name><surname>Osburga Chan</surname><given-names>P.K.</given-names></name><name><surname>Wong</surname><given-names>K.F.</given-names></name><name><surname>Cheng</surname><given-names>F.</given-names></name></person-group><article-title>High-dose <italic>N</italic>-acetylcysteine therapy for novel H1N1 influenza pneumonia</article-title><source>Ann. Intern. Med.</source><year>2010</year><volume>152</volume><fpage>687</fpage><lpage>688</lpage><pub-id pub-id-type="doi">10.7326/0003-4819-152-10-201005180-00017</pub-id><pub-id pub-id-type="pmid">20479037</pub-id></element-citation></ref><ref id="B54-molecules-16-02032"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cai</surname><given-names>J.</given-names></name><name><surname>Chen</surname><given-names>Y.</given-names></name><name><surname>Seth</surname><given-names>S.</given-names></name><name><surname>Furukawa</surname><given-names>S.</given-names></name><name><surname>Compans</surname><given-names>R.W.</given-names></name><name><surname>Jones</surname><given-names>D.P.</given-names></name></person-group><article-title>Inhibition of influenza infection by glutathione</article-title><source>Free Radic. Biol. Med.</source><year>2003</year><volume>34</volume><fpage>928</fpage><lpage>936</lpage><pub-id pub-id-type="doi">10.1016/S0891-5849(03)00023-6</pub-id><pub-id pub-id-type="pmid">12654482</pub-id></element-citation></ref><ref id="B55-molecules-16-02032"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nencioni</surname><given-names>L.</given-names></name><name><surname>Iuvara</surname><given-names>A.</given-names></name><name><surname>Aquilano</surname><given-names>K.</given-names></name><name><surname>Ciriolo</surname><given-names>M.R.</given-names></name><name><surname>Cozzolino</surname><given-names>F.</given-names></name><name><surname>Rotilio</surname><given-names>G.</given-names></name><name><surname>Garaci</surname><given-names>E.</given-names></name><name><surname>Palamara</surname><given-names>A.T.</given-names></name></person-group><article-title>Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2</article-title><source>FASEB J.</source><year>2003</year><volume>17</volume><fpage>758</fpage><lpage>760</lpage><pub-id pub-id-type="doi">10.1096/fj.02-0508fje</pub-id><pub-id pub-id-type="pmid">12594179</pub-id></element-citation></ref><ref id="B56-molecules-16-02032"><label>56.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Floriano-Sanchez</surname><given-names>E.</given-names></name><name><surname>Villanueva</surname><given-names>C.</given-names></name><name><surname>Medina-Campos</surname><given-names>O.N.</given-names></name><name><surname>Rocha</surname><given-names>D.</given-names></name><name><surname>Sanchez-Gonzalez</surname><given-names>D.J.</given-names></name><name><surname>Cardenas-Rodriguez</surname><given-names>N.</given-names></name><name><surname>Pedraza-Chaverri</surname><given-names>J.</given-names></name></person-group><article-title>Nordihydroguaiaretic acid is a potent <italic>in vitro</italic> scavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and prevents <italic>in vivo</italic> ozone-induced tyrosine nitration in lungs</article-title><source>Free Radic. Res.</source><year>2006</year><volume>40</volume><fpage>523</fpage><lpage>533</lpage><pub-id pub-id-type="doi">10.1080/10715760500419365</pub-id><pub-id pub-id-type="pmid">16551579</pub-id></element-citation></ref><ref id="B57-molecules-16-02032"><label>57.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lü</surname><given-names>J.M.</given-names></name><name><surname>Nurko</surname><given-names>J.</given-names></name><name><surname>Weakley</surname><given-names>S.M.</given-names></name><name><surname>Jiang</surname><given-names>J.</given-names></name><name><surname>Kougias</surname><given-names>P.</given-names></name><name><surname>Lin</surname><given-names>P.H.</given-names></name><name><surname>Yao</surname><given-names>Q.</given-names></name><name><surname>Chen</surname><given-names>C.</given-names></name></person-group><article-title>Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: An update</article-title><source>Med. Sci. Monit.</source><year>2010</year><volume>16</volume><fpage>RA93</fpage><lpage>RA100</lpage><pub-id pub-id-type="pmid">20424564</pub-id></element-citation></ref><ref id="B58-molecules-16-02032"><label>58.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Uchide</surname><given-names>N.</given-names></name><name><surname>Ohyama</surname><given-names>K.</given-names></name><name><surname>Bessho</surname><given-names>T.</given-names></name><name><surname>Toyoda</surname><given-names>H.</given-names></name></person-group><article-title>Inhibition of influenza virus-induced apoptosis in chorion cells of human fetal membranes by nordihydroguaiaretic acid</article-title><source>Intervirology</source><year>2005</year><volume>48</volume><fpage>336</fpage><lpage>340</lpage><pub-id pub-id-type="doi">10.1159/000085103</pub-id><pub-id pub-id-type="pmid">15956802</pub-id></element-citation></ref><ref id="B59-molecules-16-02032"><label>59.</label><element-citation publication-type="patent"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>Q.</given-names></name><name><surname>Andrea</surname><given-names>B.J.</given-names></name></person-group><article-title>Scalable synthetic process for making terameprocol</article-title><patent>WO/2010/014936</patent><day>4</day><month>2</month><year>2010</year></element-citation></ref><ref id="B60-molecules-16-02032"><label>60.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Eads</surname><given-names>D.</given-names></name><name><surname>Hansen</surname><given-names>R.</given-names></name><name><surname>Oyegunwa</surname><given-names>A.</given-names></name><name><surname>Cecil</surname><given-names>C.</given-names></name><name><surname>Culver</surname><given-names>C.</given-names></name><name><surname>Scholle</surname><given-names>F.</given-names></name><name><surname>Petty</surname><given-names>I.</given-names></name><name><surname>Laster</surname><given-names>S.</given-names></name></person-group><article-title>Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines</article-title><source>J. Inflamm. (Lond.)</source><year>2009</year><volume>6</volume><fpage>2</fpage><pub-id pub-id-type="doi">10.1186/1476-9255-6-2</pub-id><pub-id pub-id-type="pmid">19133137</pub-id></element-citation></ref><ref id="B61-molecules-16-02032"><label>61.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Craigo</surname><given-names>J.</given-names></name><name><surname>Callahan</surname><given-names>M.</given-names></name><name><surname>Huang</surname><given-names>R.C.</given-names></name><name><surname>DeLucia</surname><given-names>A.L.</given-names></name></person-group><article-title>Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives</article-title><source>Antivir. Res.</source><year>2000</year><volume>47</volume><fpage>19</fpage><lpage>28</lpage><pub-id pub-id-type="doi">10.1016/S0166-3542(00)00089-9</pub-id><pub-id pub-id-type="pmid">10930643</pub-id></element-citation></ref><ref id="B62-molecules-16-02032"><label>62.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tagaya</surname><given-names>M.</given-names></name><name><surname>Henomatsu</surname><given-names>N.</given-names></name><name><surname>Yoshimori</surname><given-names>T.</given-names></name><name><surname>Yamamoto</surname><given-names>A.</given-names></name><name><surname>Tashiro</surname><given-names>Y.</given-names></name><name><surname>Mizushima</surname><given-names>S.</given-names></name></person-group><article-title>Inhibition of vesicle-mediated protein transport by nordihydroguaiaretic acid</article-title><source>J. Biochem.</source><year>1996</year><volume>119</volume><fpage>863</fpage><lpage>869</lpage><pub-id pub-id-type="doi">10.1093/oxfordjournals.jbchem.a021323</pub-id><pub-id pub-id-type="pmid">8797085</pub-id></element-citation></ref><ref id="B63-molecules-16-02032"><label>63.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nozoe</surname><given-names>T.</given-names></name></person-group><article-title>Uber die farbstoffe im holzteile des “Hinoki” baumes. I. hinokitin und hinokitiol</article-title><source>Bull. Chem. Soc. Jpn.</source><year>1936</year><volume>11</volume><fpage>295</fpage><lpage>298</lpage><pub-id pub-id-type="doi">10.1246/bcsj.11.295</pub-id></element-citation></ref><ref id="B64-molecules-16-02032"><label>64.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Miyamoto</surname><given-names>D.</given-names></name><name><surname>Kusagaya</surname><given-names>Y.</given-names></name><name><surname>Endo</surname><given-names>N.</given-names></name><name><surname>Sometani</surname><given-names>A.</given-names></name><name><surname>Takeo</surname><given-names>S.</given-names></name><name><surname>Suzuki</surname><given-names>T.</given-names></name><name><surname>Arima</surname><given-names>Y.</given-names></name><name><surname>Nakajima</surname><given-names>K.</given-names></name><name><surname>Suzuki</surname><given-names>Y.</given-names></name></person-group><article-title>Thujaplicin-copper chelates inhibit replication of human influenza viruses</article-title><source>Antivir. Res.</source><year>1998</year><volume>39</volume><fpage>89</fpage><lpage>100</lpage><pub-id pub-id-type="doi">10.1016/S0166-3542(98)00034-5</pub-id><pub-id pub-id-type="pmid">9806486</pub-id></element-citation></ref><ref id="B65-molecules-16-02032"><label>65.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Arima</surname><given-names>Y.</given-names></name><name><surname>Hatanaka</surname><given-names>A.</given-names></name><name><surname>Tsukihara</surname><given-names>S.</given-names></name><name><surname>Fujimoto</surname><given-names>K.</given-names></name><name><surname>Fukuda</surname><given-names>K.</given-names></name><name><surname>Sakurai</surname><given-names>H.</given-names></name></person-group><article-title>Scavenging activities of α-, β- and γ-thujaplicins against active oxygen species</article-title><source>Chem. Pharm. Bull.</source><year>1997</year><volume>45</volume><fpage>1881</fpage><lpage>1886</lpage><pub-id pub-id-type="doi">10.1248/cpb.45.1881</pub-id></element-citation></ref><ref id="B66-molecules-16-02032"><label>66.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martinez</surname><given-names>J.</given-names></name><name><surname>Moreno</surname><given-names>J.J.</given-names></name></person-group><article-title>Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production</article-title><source>Biochem. Pharmacol.</source><year>2000</year><volume>59</volume><fpage>865</fpage><lpage>870</lpage><pub-id pub-id-type="doi">10.1016/S0006-2952(99)00380-9</pub-id><pub-id pub-id-type="pmid">10718345</pub-id></element-citation></ref><ref id="B67-molecules-16-02032"><label>67.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Palamara</surname><given-names>A.T.</given-names></name><name><surname>Nencioni</surname><given-names>L.</given-names></name><name><surname>Aquilano</surname><given-names>K.</given-names></name><name><surname>De Chiara</surname><given-names>G.</given-names></name><name><surname>Hernandez</surname><given-names>L.</given-names></name><name><surname>Cozzolino</surname><given-names>F.</given-names></name><name><surname>Ciriolo</surname><given-names>M.R.</given-names></name><name><surname>Garaci</surname><given-names>E.</given-names></name></person-group><article-title>Inhibition of influenza A virus replication by resveratrol</article-title><source>J. Infect. Dis.</source><year>2005</year><volume>191</volume><fpage>1719</fpage><lpage>1729</lpage><pub-id pub-id-type="doi">10.1086/429694</pub-id><pub-id pub-id-type="pmid">15838800</pub-id></element-citation></ref><ref id="B68-molecules-16-02032"><label>68.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>Y.L.</given-names></name><name><surname>Loke</surname><given-names>S.H.</given-names></name><name><surname>Hsu</surname><given-names>C.C.</given-names></name><name><surname>Chiou</surname><given-names>W.F.</given-names></name></person-group><article-title>(+)-Vitisin A inhibits influenza A virus-induced RANTES production in A549 alveolar epithelial cells through interference with Akt and STAT1 phosphorylation</article-title><source>Planta Med.</source><year>2008</year><volume>74</volume><fpage>156</fpage><lpage>162</lpage><pub-id pub-id-type="doi">10.1055/s-2007-993786</pub-id><pub-id pub-id-type="pmid">18240103</pub-id></element-citation></ref><ref id="B69-molecules-16-02032"><label>69.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>Y.L.</given-names></name><name><surname>Tsai</surname><given-names>W.J.</given-names></name><name><surname>Shen</surname><given-names>C.C.</given-names></name><name><surname>Chen</surname><given-names>C.C.</given-names></name></person-group><article-title>Resveratrol derivatives from the roots of <italic>Vitis thunbergii</italic></article-title><source>J. Nat. Prod.</source><year>2005</year><volume>68</volume><fpage>217</fpage><lpage>220</lpage><pub-id pub-id-type="doi">10.1021/np049686p</pub-id><pub-id pub-id-type="pmid">15730246</pub-id></element-citation></ref><ref id="B70-molecules-16-02032"><label>70.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>García-Alonso</surname><given-names>M.</given-names></name><name><surname>Rimbach</surname><given-names>G.</given-names></name><name><surname>Rivas-Gonzalo</surname><given-names>J.C.</given-names></name><name><surname>De Pascual-Teresa</surname><given-names>S.</given-names></name></person-group><article-title>Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A - studies in platelets, monocytes, and human endothelial cells</article-title><source>J. Agric. Food Chem.</source><year>2004</year><volume>52</volume><fpage>3378</fpage><lpage>3384</lpage><pub-id pub-id-type="doi">10.1021/jf035360v</pub-id><pub-id pub-id-type="pmid">15161201</pub-id></element-citation></ref><ref id="B71-molecules-16-02032"><label>71.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>K.S.</given-names></name><name><surname>Lin</surname><given-names>M.</given-names></name><name><surname>Cheng</surname><given-names>G.F.</given-names></name></person-group><article-title>Anti-inflammatory tetramers of resveratrol from the roots of <italic>Vitis amurensis</italic> and the conformations of the seven-membered ring in some oligostilbenes</article-title><source>Phytochemistry</source><year>2001</year><volume>58</volume><fpage>357</fpage><lpage>362</lpage><pub-id pub-id-type="doi">10.1016/S0031-9422(01)00224-2</pub-id><pub-id pub-id-type="pmid">11551564</pub-id></element-citation></ref><ref id="B72-molecules-16-02032"><label>72.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>Y.L.</given-names></name><name><surname>Loke</surname><given-names>S.H.</given-names></name><name><surname>Hsu</surname><given-names>C.C.</given-names></name><name><surname>Chiou</surname><given-names>W.F.</given-names></name></person-group><article-title>(+)-Vitisin A inhibits influenza A virus-induced RANTES production in A549 alveolar epithelial cells through interference with Akt and STAT1 phosphorylation</article-title><source>Planta Med.</source><year>2008</year><volume>74</volume><fpage>156</fpage><lpage>162</lpage><pub-id pub-id-type="doi">10.1055/s-2007-993786</pub-id><pub-id pub-id-type="pmid">18240103</pub-id></element-citation></ref><ref id="B73-molecules-16-02032"><label>73.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Germouty</surname><given-names>J.</given-names></name><name><surname>Jirou-Najou</surname><given-names>J.L.</given-names></name></person-group><article-title>Clinical efficacy of ambroxol in the treatment of bronchial stasis. Clinical trial in 120 patients at two different doses</article-title><source>Respiration</source><year>1987</year><volume>51</volume><fpage>37</fpage><lpage>41</lpage><pub-id pub-id-type="doi">10.1159/000195273</pub-id><pub-id pub-id-type="pmid">3299566</pub-id></element-citation></ref><ref id="B74-molecules-16-02032"><label>74.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yang</surname><given-names>B.</given-names></name><name><surname>Yao</surname><given-names>D.F.</given-names></name><name><surname>Ohuchi</surname><given-names>M.</given-names></name><name><surname>Ide</surname><given-names>M.</given-names></name><name><surname>Yano</surname><given-names>M.</given-names></name><name><surname>Okumura</surname><given-names>Y.</given-names></name><name><surname>Kido</surname><given-names>H.</given-names></name></person-group><article-title>Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels</article-title><source>Eur. Respir. J.</source><year>2002</year><volume>19</volume><fpage>952</fpage><lpage>958</lpage><pub-id pub-id-type="doi">10.1183/09031936.02.00253302</pub-id><pub-id pub-id-type="pmid">12030738</pub-id></element-citation></ref><ref id="B75-molecules-16-02032"><label>75.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gillissen</surname><given-names>A.</given-names></name><name><surname>Bartling</surname><given-names>A.</given-names></name><name><surname>Schoen</surname><given-names>S.</given-names></name><name><surname>Schultze-Werninghaus</surname><given-names>G.</given-names></name></person-group><article-title>Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells <italic>in vitro</italic></article-title><source>Lung</source><year>1997</year><volume>175</volume><fpage>235</fpage><lpage>242</lpage><pub-id pub-id-type="doi">10.1007/PL00007570</pub-id><pub-id pub-id-type="pmid">9195551</pub-id></element-citation></ref><ref id="B76-molecules-16-02032"><label>76.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gillissen</surname><given-names>A.</given-names></name><name><surname>Schärling</surname><given-names>B.</given-names></name><name><surname>Jaworska</surname><given-names>M.</given-names></name><name><surname>Bartling</surname><given-names>A.</given-names></name><name><surname>Rasche</surname><given-names>K.</given-names></name><name><surname>Schultze-Werninghaus</surname><given-names>G.</given-names></name></person-group><article-title>Oxidant scavenger function of ambroxol <italic>in vitro</italic>: A comparison with <italic>N</italic>-acetylcysteine</article-title><source>Res. Exp. Med. (Berl.)</source><year>1997</year><volume>196</volume><fpage>389</fpage><lpage>398</lpage><pub-id pub-id-type="doi">10.1007/s004330050049</pub-id><pub-id pub-id-type="pmid">9089888</pub-id></element-citation></ref><ref id="B77-molecules-16-02032"><label>77.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nobata</surname><given-names>K.</given-names></name><name><surname>Fujimura</surname><given-names>M.</given-names></name><name><surname>Ishiura</surname><given-names>Y.</given-names></name><name><surname>Myou</surname><given-names>S.</given-names></name><name><surname>Nakao</surname><given-names>S.</given-names></name></person-group><article-title>Ambroxol for the prevention of acute upper respiratory disease</article-title><source>Clin. Exp. Med.</source><year>2006</year><volume>6</volume><fpage>79</fpage><lpage>83</lpage><pub-id pub-id-type="doi">10.1007/s10238-006-0099-2</pub-id><pub-id pub-id-type="pmid">16820995</pub-id></element-citation></ref><ref id="B78-molecules-16-02032"><label>78.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tsujimoto</surname><given-names>Y.</given-names></name><name><surname>Hashizume</surname><given-names>H.</given-names></name><name><surname>Yamazaki</surname><given-names>M.</given-names></name></person-group><article-title>Superoxide radical scavenging activity of phenolic compounds</article-title><source>Int. J. Biochem.</source><year>1993</year><volume>25</volume><fpage>491</fpage><lpage>494</lpage><pub-id pub-id-type="pmid">8385635</pub-id></element-citation></ref><ref id="B79-molecules-16-02032"><label>79.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jariwalla</surname><given-names>R.J.</given-names></name><name><surname>Roomi</surname><given-names>M.W.</given-names></name><name><surname>Gangapurkar</surname><given-names>B.</given-names></name><name><surname>Kalinovsky</surname><given-names>T.</given-names></name><name><surname>Niedzwiecki</surname><given-names>A.</given-names></name><name><surname>Rath</surname><given-names>M.</given-names></name></person-group><article-title>Suppression of influenza A virus nuclear antigen production and neuraminidase activity by a nutrient mixture containing ascorbic acid, green tea extract and amino acids</article-title><source>Biofactors</source><year>2007</year><volume>31</volume><fpage>1</fpage><lpage>15</lpage><pub-id pub-id-type="doi">10.1002/biof.5520310101</pub-id><pub-id pub-id-type="pmid">18806304</pub-id></element-citation></ref><ref id="B80-molecules-16-02032"><label>80.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Furuya</surname><given-names>A.</given-names></name><name><surname>Uozaki</surname><given-names>M.</given-names></name><name><surname>Yamasaki</surname><given-names>H.</given-names></name><name><surname>Arakawa</surname><given-names>T.</given-names></name><name><surname>Arita</surname><given-names>M.</given-names></name><name><surname>Koyama</surname><given-names>A.H.</given-names></name></person-group><article-title>Antiviral effects of ascorbic and dehydroascorbic acids <italic>in vitro</italic></article-title><source>Int. J. Mol. Med.</source><year>2008</year><volume>22</volume><fpage>541</fpage><lpage>545</lpage><pub-id pub-id-type="pmid">18813862</pub-id></element-citation></ref><ref id="B81-molecules-16-02032"><label>81.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kimbarowski</surname><given-names>J.A.</given-names></name><name><surname>Mokrow</surname><given-names>N.J.</given-names></name></person-group><article-title>Colored precipitation reaction of the urine according to Kimbarowski (FARK) as an index of the effect of ascorbic acid during treatment of viral influenza</article-title><source>Dtsch. Gesundheitsw.</source><year>1967</year><volume>22</volume><fpage>2413</fpage><lpage>2418</lpage><pub-id pub-id-type="pmid">5614915</pub-id></element-citation></ref><ref id="B82-molecules-16-02032"><label>82.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Banerjee</surname><given-names>D.</given-names></name><name><surname>Kaul</surname><given-names>D.</given-names></name></person-group><article-title>Combined inhalational and oral supplementation of ascorbic acid may prevent influenza pandemic emergency: A hypothesis</article-title><source>Nutrition</source><year>2010</year><volume>26</volume><fpage>128</fpage><lpage>132</lpage><pub-id pub-id-type="doi">10.1016/j.nut.2009.09.015</pub-id><pub-id pub-id-type="pmid">20005468</pub-id></element-citation></ref><ref id="B83-molecules-16-02032"><label>83.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Robak</surname><given-names>J.</given-names></name><name><surname>Gryglewski</surname><given-names>R.J.</given-names></name></person-group><article-title>Bioactivity of flavonoids</article-title><source>Pol. J. Pharmacol.</source><year>1996</year><volume>48</volume><fpage>555</fpage><lpage>564</lpage><pub-id pub-id-type="pmid">9112694</pub-id></element-citation></ref><ref id="B84-molecules-16-02032"><label>84.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagai</surname><given-names>T.</given-names></name><name><surname>Miyaichi</surname><given-names>Y.</given-names></name><name><surname>Tomimori</surname><given-names>T.</given-names></name><name><surname>Yamada</surname><given-names>H.</given-names></name></person-group><article-title>Inhibition of mouse liver sialidase by plant flavonoids</article-title><source>Biochem. Biophys. Res. Commun.</source><year>1989</year><volume>163</volume><fpage>25</fpage><lpage>31</lpage><pub-id pub-id-type="doi">10.1016/0006-291X(89)92093-7</pub-id><pub-id pub-id-type="pmid">2775264</pub-id></element-citation></ref><ref id="B85-molecules-16-02032"><label>85.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagai</surname><given-names>T.</given-names></name><name><surname>Miyaichi</surname><given-names>Y.</given-names></name><name><surname>Tomimori</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>Y.</given-names></name><name><surname>Yamada</surname><given-names>H.</given-names></name></person-group><article-title>Inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids</article-title><source>Chem. Pharm. Bull. (Tokyo)</source><year>1990</year><volume>38</volume><fpage>1329</fpage><lpage>1332</lpage><pub-id pub-id-type="doi">10.1248/cpb.38.1329</pub-id><pub-id pub-id-type="pmid">2393958</pub-id></element-citation></ref><ref id="B86-molecules-16-02032"><label>86.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagai</surname><given-names>T.</given-names></name><name><surname>Miyaichi</surname><given-names>Y.</given-names></name><name><surname>Tomimori</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>Y.</given-names></name><name><surname>Yamada</surname><given-names>H.</given-names></name></person-group><article-title><italic>In vivo</italic> anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase</article-title><source>Antivir. Res.</source><year>1992</year><volume>19</volume><fpage>207</fpage><lpage>217</lpage><pub-id pub-id-type="doi">10.1016/0166-3542(92)90080-O</pub-id><pub-id pub-id-type="pmid">1444327</pub-id></element-citation></ref><ref id="B87-molecules-16-02032"><label>87.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagai</surname><given-names>T.</given-names></name><name><surname>Suzuki</surname><given-names>Y.</given-names></name><name><surname>Tomimori</surname><given-names>T.</given-names></name><name><surname>Yamada</surname><given-names>H.</given-names></name></person-group><article-title>Antiviral activity of plant flavonoid, 5,7,4’-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis against influenza A (H3N2) and B viruses</article-title><source>Biol. Pharm. Bull.</source><year>1995</year><volume>18</volume><fpage>295</fpage><lpage>299</lpage><pub-id pub-id-type="doi">10.1248/bpb.18.295</pub-id><pub-id pub-id-type="pmid">7742801</pub-id></element-citation></ref><ref id="B88-molecules-16-02032"><label>88.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nagai</surname><given-names>T.</given-names></name><name><surname>Moriguchi</surname><given-names>R.</given-names></name><name><surname>Suzuki</surname><given-names>Y.</given-names></name><name><surname>Tomimori</surname><given-names>T.</given-names></name><name><surname>Yamada</surname><given-names>H.</given-names></name></person-group><article-title>Mode of action of the anti-influenza virus activity of plant flavonoid, 5,7,4’-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis</article-title><source>Antivir. Res.</source><year>1995</year><volume>26</volume><fpage>11</fpage><lpage>25</lpage><pub-id pub-id-type="doi">10.1016/0166-3542(94)00062-D</pub-id><pub-id pub-id-type="pmid">7741518</pub-id></element-citation></ref><ref id="B89-molecules-16-02032"><label>89.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Song</surname><given-names>J.M.</given-names></name><name><surname>Lee</surname><given-names>K.H.</given-names></name><name><surname>Seong</surname><given-names>B.L.</given-names></name></person-group><article-title>Antiviral effect of catechins in green tea on influenza virus</article-title><source>Antivir. Res.</source><year>2005</year><volume>68</volume><fpage>66</fpage><lpage>74</lpage><pub-id pub-id-type="doi">10.1016/j.antiviral.2005.06.010</pub-id><pub-id pub-id-type="pmid">16137775</pub-id></element-citation></ref><ref id="B90-molecules-16-02032"><label>90.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kashima</surname><given-names>M.</given-names></name></person-group><article-title>Effects of catechins on superoxide and hydroxyl radical</article-title><source>Chem. Pharm. Bull. (Tokyo)</source><year>1999</year><volume>47</volume><fpage>279</fpage><lpage>283</lpage><pub-id pub-id-type="doi">10.1248/cpb.47.279</pub-id><pub-id pub-id-type="pmid">10071858</pub-id></element-citation></ref><ref id="B91-molecules-16-02032"><label>91.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yamada</surname><given-names>H.</given-names></name><name><surname>Takuma</surname><given-names>N.</given-names></name><name><surname>Daimon</surname><given-names>T.</given-names></name><name><surname>Hara</surname><given-names>Y.</given-names></name></person-group><article-title>Gargling with tea catechin extracts for the prevention of influenza infection in elderly nursing home residents: A prospective clinical study</article-title><source>J. Altern. Complement. Med.</source><year>2006</year><volume>12</volume><fpage>669</fpage><lpage>672</lpage><pub-id pub-id-type="doi">10.1089/acm.2006.12.669</pub-id><pub-id pub-id-type="pmid">16970537</pub-id></element-citation></ref><ref id="B92-molecules-16-02032"><label>92.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mori</surname><given-names>S.</given-names></name><name><surname>Miyake</surname><given-names>S.</given-names></name><name><surname>Kobe</surname><given-names>T.</given-names></name><name><surname>Nakaya</surname><given-names>T.</given-names></name><name><surname>Fuller</surname><given-names>S.D.</given-names></name><name><surname>Kato</surname><given-names>N.</given-names></name><name><surname>Kaihatsu</surname><given-names>K.</given-names></name></person-group><article-title>Enhanced anti-influenza A virus activity of (-)-epigallocatechin-3-<italic>O</italic>-gallate fatty acid monoester derivatives: Effect of alkyl chain length</article-title><source>Bioorg. Med. Chem. Lett.</source><year>2008</year><volume>18</volume><fpage>4249</fpage><lpage>4952</lpage><pub-id pub-id-type="doi">10.1016/j.bmcl.2008.02.020</pub-id><pub-id pub-id-type="pmid">18547804</pub-id></element-citation></ref><ref id="B93-molecules-16-02032"><label>93.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuzuhara</surname><given-names>T.</given-names></name><name><surname>Iwai</surname><given-names>Y.</given-names></name><name><surname>Takahashi</surname><given-names>H.</given-names></name><name><surname>Hatakeyama</surname><given-names>D.</given-names></name><name><surname>Echigo</surname><given-names>N.</given-names></name></person-group><article-title>Green tea catechins inhibit the endonuclease activity of influenza A virus RNA polymerase</article-title><source>PLoS. Curr.</source><year>2009</year><volume>1</volume><elocation-id>RRN1052</elocation-id><pub-id pub-id-type="doi">10.1371/currents.RRN1052</pub-id><pub-id pub-id-type="pmid">20025206</pub-id></element-citation></ref><ref id="B94-molecules-16-02032"><label>94.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>H.J.</given-names></name><name><surname>Song</surname><given-names>J.H.</given-names></name><name><surname>Park</surname><given-names>K.S.</given-names></name><name><surname>Kwon</surname><given-names>D.H.</given-names></name></person-group><article-title>Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication</article-title><source>Eur. J. Pharm. Sci.</source><year>2009</year><volume>37</volume><fpage>329</fpage><lpage>333</lpage><pub-id pub-id-type="doi">10.1016/j.ejps.2009.03.002</pub-id><pub-id pub-id-type="pmid">19491023</pub-id></element-citation></ref><ref id="B95-molecules-16-02032"><label>95.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>Y.</given-names></name><name><surname>Narayanan</surname><given-names>S.</given-names></name><name><surname>Chang</surname><given-names>K.O.</given-names></name></person-group><article-title>Inhibition of influenza virus replication by plant-derived isoquercetin</article-title><source>Antivir. Res.</source><year>2010</year><volume>88</volume><fpage>227</fpage><lpage>235</lpage><pub-id pub-id-type="doi">10.1016/j.antiviral.2010.08.016</pub-id><pub-id pub-id-type="pmid">20826184</pub-id></element-citation></ref><ref id="B96-molecules-16-02032"><label>96.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fujii</surname><given-names>H.</given-names></name><name><surname>Sun</surname><given-names>B.</given-names></name><name><surname>Nishioka</surname><given-names>H.</given-names></name><name><surname>Hirose</surname><given-names>A.</given-names></name><name><surname>Aruoma</surname><given-names>O.I.</given-names></name></person-group><article-title>Evaluation of the safety and toxicity of the oligomerized polyphenol Oligonol</article-title><source>Food Chem. Toxicol.</source><year>2007</year><volume>45</volume><fpage>378</fpage><lpage>387</lpage><pub-id pub-id-type="doi">10.1016/j.fct.2006.08.026</pub-id><pub-id pub-id-type="pmid">17081671</pub-id></element-citation></ref><ref id="B97-molecules-16-02032"><label>97.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gangehei</surname><given-names>L.</given-names></name><name><surname>Ali</surname><given-names>M.</given-names></name><name><surname>Zhang</surname><given-names>W.</given-names></name><name><surname>Chen</surname><given-names>Z.</given-names></name><name><surname>Wakame</surname><given-names>K.</given-names></name><name><surname>Haidari</surname><given-names>M.</given-names></name></person-group><article-title>Oligonol a low molecular weight polyphenol of lychee fruit extract inhibits proliferation of influenza virus by blocking reactive oxygen species-dependent ERK phosphorylation</article-title><source>Phytomedicine</source><year>2010</year><volume>17</volume><fpage>1047</fpage><lpage>1056</lpage><pub-id pub-id-type="doi">10.1016/j.phymed.2010.03.016</pub-id><pub-id pub-id-type="pmid">20554190</pub-id></element-citation></ref></ref-list></back><floats-group><fig id="molecules-16-02032-f001" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Current available anti-influenza drugs.</p></caption><graphic xlink:href="molecules-16-02032-g001"></graphic></fig><fig id="molecules-16-02032-f002" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Tissue injury model during influenza virus infection.</p></caption><graphic xlink:href="molecules-16-02032-g002"></graphic></fig><fig id="molecules-16-02032-f003" orientation="portrait" position="float"><label>Figure 3</label><caption><p>Thiol antioxidants with anti-influenza virus activity.</p></caption><graphic xlink:href="molecules-16-02032-g003"></graphic></fig><fig id="molecules-16-02032-f004" orientation="portrait" position="float"><label>Figure 4</label><caption><p>Hydroxyl antioxidants with anti-influenza virus activity.</p></caption><graphic xlink:href="molecules-16-02032-g004"></graphic></fig><fig id="molecules-16-02032-f005" orientation="portrait" position="float"><label>Figure 5</label><caption><p>Flavonoids with anti-influenza virus activity.</p></caption><graphic xlink:href="molecules-16-02032-g005"></graphic></fig><table-wrap id="molecules-16-02032-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">molecules-16-02032-t001_Table 1</object-id><label>Table 1</label><caption><p>Composition of oligonol and lychee fruit polyphenol.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Name</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Oligonol</th><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Lychee fruit polyphenol</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Monomer</td><td align="left" valign="top" rowspan="1" colspan="1">(+)-Catechin</td><td align="left" valign="top" rowspan="1" colspan="1">0.1%></td><td align="left" valign="top" rowspan="1" colspan="1">0.1%></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">(-)-Epicatechin</td><td align="left" valign="top" rowspan="1" colspan="1">7.5%</td><td align="left" valign="top" rowspan="1" colspan="1">6.4%</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">(-)-ECG</td><td align="left" valign="top" rowspan="1" colspan="1">2.1%</td><td align="left" valign="top" rowspan="1" colspan="1">n.d.</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Dimer</td><td align="left" valign="top" rowspan="1" colspan="1">Procyanidin A1</td><td align="left" valign="top" rowspan="1" colspan="1">4.2%</td><td align="left" valign="top" rowspan="1" colspan="1">4.0%</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Procyanidin A2</td><td align="left" valign="top" rowspan="1" colspan="1">5.1%</td><td align="left" valign="top" rowspan="1" colspan="1">3.3%</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Procyanidin B1</td><td align="left" valign="top" rowspan="1" colspan="1">1.4%</td><td align="left" valign="top" rowspan="1" colspan="1">0.8%</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="left" valign="top" rowspan="1" colspan="1">Procyanidin B2</td><td align="left" valign="top" rowspan="1" colspan="1">2.9%</td><td align="left" valign="top" rowspan="1" colspan="1">1.7%</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Trimer</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">(-)-Epicatechin-(4β→8,2β→<italic>o</italic>-7)-epicatechin-(4β→8)-epicatechin</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">4.0%</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">3.6%</td></tr></tbody></table><table-wrap-foot><fn><p>Abbreviation: n.d., not detected.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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