{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:43:49Z","timestamp":1773089029893,"version":"3.50.1"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2011,2,28]],"date-time":"2011-02-28T00:00:00Z","timestamp":1298851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats: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, N-acetyl-L-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.<\/jats:p>","DOI":"10.3390\/molecules16032032","type":"journal-article","created":{"date-parts":[[2011,3,1]],"date-time":"2011-03-01T15:44:36Z","timestamp":1298994276000},"page":"2032-2052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications"],"prefix":"10.3390","volume":"16","author":[{"given":"Noboru","family":"Uchide","sequence":"first","affiliation":[{"name":"Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroo","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2011,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1002\/eji.200939911","article-title":"A novel H1N1 virus causes the first pandemic of the 21st century","volume":"39","author":"Peiris","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/S0929-6646(09)60369-7","article-title":"Novel swine-origin influenza virus A (H1N1): The first pandemic of the 21st century","volume":"108","author":"Chang","year":"2009","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1097\/CCM.0b013e3181c92eeb","article-title":"Complications of seasonal and pandemic influenza","volume":"38","author":"Rothberg","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.1016\/j.vaccine.2010.05.031","article-title":"The 2009 A (H1N1) influenza virus pandemic: A review","volume":"28","author":"Girard","year":"2010","journal-title":"Vaccine"},{"key":"ref_5","unstructured":"World Health Organization (2011, February 26). Pandemic (H1N1) 2009 - update 111, Available online: http:\/\/www.who.int\/csr\/ don\/2010_07_30\/en\/index.html."},{"key":"ref_6","unstructured":"World Health Organization (2011, February 26). Influenza updates, Available online: http:\/\/www.who.int\/csr\/don\/2010_09_10\/ en\/index.html."},{"key":"ref_7","unstructured":"Kamps, B.S., Hoffmann, C., and Preiser, W. (2006). Influenza. Influenza Report, Flying Publishers."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.antiviral.2008.01.003","article-title":"Current and future antiviral therapy of severe seasonal and avian influenza","volume":"78","author":"Beigel","year":"2008","journal-title":"Antivir. Res."},{"key":"ref_9","unstructured":"Centers for Disease Control and Prevention (CDC) (2009). Update: Drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb. Mortal. Wkly. Rep., 58, 433\u2013435."},{"key":"ref_10","unstructured":"World Health Organization (2011, February 26). Pandemic (H1N1) 2009 - update 60, Available online: http:\/\/www.who.int\/csr\/ don\/2009_08_04\/en\/index.html."},{"key":"ref_11","unstructured":"World Health Organization (2010). Update on oseltamivir-resistant pandemic A (H1N1) 2009 influenza virus: January 2010. Wkly. Epidemiol. Rec., 85, 37\u201340."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1128\/AAC.01755-09","article-title":"Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection","volume":"54","author":"Sugaya","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.2174\/157489110791233513","article-title":"Treatment of severe cases of pandemic (H1N1) 2009 influenza: Review of antivirals and adjuvant therapy","volume":"5","author":"Bearman","year":"2010","journal-title":"Recent Patents Antiinfect. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1164\/ajrccm.182.9.1209","article-title":"Peramivir for severe influenza infection in a patient with diabetic nephropathy","volume":"182","author":"Nasu","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1399-3062.2010.00582.x","article-title":"Early emergence of an H275Y mutation in a hematopoietic cell transplant recipient treated with intravenous peramivir","volume":"12","author":"Renaud","year":"2010","journal-title":"Transpl. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.hrtlng.2010.04.003","article-title":"Fulminant fatal swine influenza (H1N1): Myocarditis, myocardial infarction, or severe influenza pneumonia?","volume":"39","author":"Cunha","year":"2010","journal-title":"Heart Lung"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nguyen, J.T., Hoopes, J.D., Le, M.H., Smee, D.F., Patick, A.K., Faix, D.J., Blair, P.J., de Jong, M.D., Prichard, M.N., and Went, G.T. (2010). Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro. PLoS One, 5.","DOI":"10.1371\/journal.pone.0009332"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"14933","DOI":"10.1128\/JVI.79.23.14933-14944.2005","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","volume":"79","author":"Tumpey","year":"2005","journal-title":"J. Virol."},{"key":"ref_19","first-page":"295","article-title":"Current status of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection","volume":"1","author":"Uchide","year":"2007","journal-title":"Gene Regul. Syst. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3181\/00379727-217-44206","article-title":"Free radicals in viral pathogenesis: Molecular mechanisms involving superoxide and NO","volume":"217","author":"Akaike","year":"1998","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/187152108783954605","article-title":"Potential of selected antioxidants for influenza chemotherapy","volume":"7","author":"Uchide","year":"2008","journal-title":"Anti-Infect. Agents Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2174\/138955708784223530","article-title":"Future target molecules for influenza treatment","volume":"8","author":"Uchide","year":"2008","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1126\/science.2543070","article-title":"Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD","volume":"244","author":"Oda","year":"1989","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1128\/AAC.40.11.2626","article-title":"Inhibitory effects of recombinant manganese superoxide dismutase on influenza virus infections in mice","volume":"40","author":"Sidwell","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","first-page":"53","article-title":"Combined protective effect of a fungal Cu\/Zn-containing superoxide dismutase and rimantadine hydrochloride in experimental murine influenza a virus infection","volume":"47","author":"Serkedjieva","year":"2003","journal-title":"Acta Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1172\/JCI114499","article-title":"Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice","volume":"85","author":"Akaike","year":"1990","journal-title":"J. Clin. Invest."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"L69","DOI":"10.1152\/ajplung.2001.280.1.L69","article-title":"Prevention of influenza-induced lung injury in mice overexpressing extracellular superoxide dismutase","volume":"280","author":"Suliman","year":"2001","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1002\/eji.200635977","article-title":"An absence of reactive oxygen species improves the resolution of lung influenza infection","volume":"36","author":"Snelgrove","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1161\/01.ATV.21.5.739","article-title":"Increased NAD(P)H oxidase and reactive oxygen species in coronary arteries after balloon injury","volume":"21","author":"Shi","year":"2001","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/jac\/dkg282","article-title":"Antiviral function of pyrrolidine dithiocarbamate against influenza virus: The inhibition of viral gene replication and transcription","volume":"52","author":"Uchide","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0166-3542(02)00109-2","article-title":"Effect of antioxidants on apoptosis induced by influenza virus infection: Inhibition of viral gene replication and transcription with pyrrolidine dithiocarbamate","volume":"56","author":"Uchide","year":"2002","journal-title":"Antivir. Res."},{"key":"ref_32","first-page":"L134","article-title":"Role of oxidants in influenza virus-induced gene expression","volume":"274","author":"Knobil","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1006\/excr.1997.3602","article-title":"Characterization of influenza virus-induced death of J774.1 macrophages","volume":"234","author":"Lowy","year":"1997","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.virusres.2003.08.007","article-title":"Active and inactive influenza virus induction of tumor necrosis factor-\u03b1 and nitric oxide in J774.1 murine macrophages: Modulation by interferon-\u03b3 and failure to induce apoptosis","volume":"97","author":"McKinney","year":"2003","journal-title":"Virus Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.3748\/wjg.v11.i10.1508","article-title":"Activation of nuclear factor-\u03baB and effects of pyrrolidine dithiocarbamate on TNBS-induced rat colitis","volume":"11","author":"Chen","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/sj.bjp.0704463","article-title":"Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation","volume":"135","author":"Cuzzocrea","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7308","DOI":"10.3748\/wjg.v11.i46.7308","article-title":"Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine","volume":"11","author":"Mallick","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1167\/iovs.04-0640","article-title":"Effects of the NF-\u03baB inhibitor pyrrolidine dithiocarbamate on experimentally induced autoimmune anterior uveitis","volume":"46","author":"Yang","year":"2005","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0014-5793(99)00390-7","article-title":"Zinc is required in pyrrolidine dithiocarbamate inhibition of NF-\u03baB activation","volume":"449","author":"Kim","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1099\/0022-1317-23-1-59","article-title":"Inhibition of the particle-associated RNA-dependent RNA polymerase activity of influenza viruses by chelating agents","volume":"23","author":"Oxford","year":"1974","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8014","DOI":"10.1128\/JVI.79.13.8014-8023.2005","article-title":"Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through inhibition of the ubiquitin-proteasome pathway","volume":"79","author":"Si","year":"2005","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13892","DOI":"10.1128\/JVI.79.22.13892-13899.2005","article-title":"Inhibition of polyprotein processing and RNA replication of human rhinovirus by pyrrolidine dithiocarbamate involves metal ions","volume":"79","author":"Krenn","year":"2005","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000097396","article-title":"Effects of mitogen-activated protein kinase inhibitors on tumor necrosis factor-\u03b1 gene expression and apoptosis induction in cultured human fetal membrane chorion cells infected with influenza virus","volume":"50","author":"Uchide","year":"2007","journal-title":"Intervirology"},{"key":"ref_44","unstructured":"Chiou, W.F., Chen, C.C., and Wei, B.L. (2009). 8-Prenylkaempferol suppresses influenza A virus-induced RANTES production in A549 cells via blocking PI3K-mediated transcriptional activation of NF-\u03baB and IRF3. Evid. Based Complement. Altern. Med., In Press."},{"key":"ref_45","first-page":"114","article-title":"Clinical applications of N-acetylcysteine","volume":"3","author":"Kelly","year":"1998","journal-title":"Altern. Med. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1292\/jvms.58.11_1137","article-title":"Effect of brefeldin A on influenza A virus-induced apoptosis in vitro","volume":"58","author":"Saito","year":"1996","journal-title":"J. Vet. Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1006\/viro.2001.1010","article-title":"The involvement of a stress-activated pathway in equine influenza virus-mediated apoptosis","volume":"287","author":"Lin","year":"2001","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.bcp.2009.08.025","article-title":"N-acetyl-l-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus","volume":"79","author":"Geiler","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_49","first-page":"123","article-title":"Protective effect of N-acetylcysteine in a model of influenza infection in mice","volume":"13","author":"Ungheri","year":"2000","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/039463200401700114","article-title":"Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model","volume":"17","author":"Ghezzi","year":"2004","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1177\/039463200702000215","article-title":"N-acetylcysteine synergizes with oseltamivir in protecting mice from lethal influenza infection","volume":"20","author":"Garozzo","year":"2007","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1183\/09031936.97.10071535","article-title":"Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment","volume":"10","author":"Grassi","year":"1997","journal-title":"Eur. Respir. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"687","DOI":"10.7326\/0003-4819-152-10-201005180-00017","article-title":"High-dose N-acetylcysteine therapy for novel H1N1 influenza pneumonia","volume":"152","author":"Lai","year":"2010","journal-title":"Ann. Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/S0891-5849(03)00023-6","article-title":"Inhibition of influenza infection by glutathione","volume":"34","author":"Cai","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1096\/fj.02-0508fje","article-title":"Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl-2","volume":"17","author":"Nencioni","year":"2003","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/10715760500419365","article-title":"Nordihydroguaiaretic acid is a potent in vitro scavenger of peroxynitrite, singlet oxygen, hydroxyl radical, superoxide anion and hypochlorous acid and prevents in vivo ozone-induced tyrosine nitration in lungs","volume":"40","author":"Villanueva","year":"2006","journal-title":"Free Radic. Res."},{"key":"ref_57","first-page":"RA93","article-title":"Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: An update","volume":"16","author":"Nurko","year":"2010","journal-title":"Med. Sci. Monit."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1159\/000085103","article-title":"Inhibition of influenza virus-induced apoptosis in chorion cells of human fetal membranes by nordihydroguaiaretic acid","volume":"48","author":"Uchide","year":"2005","journal-title":"Intervirology"},{"key":"ref_59","unstructured":"Chen, Q., and Andrea, B.J. (2010). Scalable synthetic process for making terameprocol. (WO\/2010\/014936)."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1476-9255-6-2","article-title":"Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines","volume":"6","author":"Eads","year":"2009","journal-title":"J. Inflamm. (Lond.)"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0166-3542(00)00089-9","article-title":"Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives","volume":"47","author":"Craigo","year":"2000","journal-title":"Antivir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/oxfordjournals.jbchem.a021323","article-title":"Inhibition of vesicle-mediated protein transport by nordihydroguaiaretic acid","volume":"119","author":"Tagaya","year":"1996","journal-title":"J. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1246\/bcsj.11.295","article-title":"Uber die farbstoffe im holzteile des \u201cHinoki\u201d baumes. I. hinokitin und hinokitiol","volume":"11","author":"Nozoe","year":"1936","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0166-3542(98)00034-5","article-title":"Thujaplicin-copper chelates inhibit replication of human influenza viruses","volume":"39","author":"Miyamoto","year":"1998","journal-title":"Antivir. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1248\/cpb.45.1881","article-title":"Scavenging activities of \u03b1-, \u03b2- and \u03b3-thujaplicins against active oxygen species","volume":"45","author":"Arima","year":"1997","journal-title":"Chem. Pharm. Bull."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0006-2952(99)00380-9","article-title":"Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production","volume":"59","author":"Martinez","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1086\/429694","article-title":"Inhibition of influenza A virus replication by resveratrol","volume":"191","author":"Palamara","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1055\/s-2007-993786","article-title":"(+)-Vitisin A inhibits influenza A virus-induced RANTES production in A549 alveolar epithelial cells through interference with Akt and STAT1 phosphorylation","volume":"74","author":"Huang","year":"2008","journal-title":"Planta Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1021\/np049686p","article-title":"Resveratrol derivatives from the roots of Vitis thunbergii","volume":"68","author":"Huang","year":"2005","journal-title":"J. Nat. Prod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1021\/jf035360v","article-title":"Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A - studies in platelets, monocytes, and human endothelial cells","volume":"52","author":"Rimbach","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0031-9422(01)00224-2","article-title":"Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membered ring in some oligostilbenes","volume":"58","author":"Huang","year":"2001","journal-title":"Phytochemistry"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1055\/s-2007-993786","article-title":"(+)-Vitisin A inhibits influenza A virus-induced RANTES production in A549 alveolar epithelial cells through interference with Akt and STAT1 phosphorylation","volume":"74","author":"Huang","year":"2008","journal-title":"Planta Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000195273","article-title":"Clinical efficacy of ambroxol in the treatment of bronchial stasis. Clinical trial in 120 patients at two different doses","volume":"51","author":"Germouty","year":"1987","journal-title":"Respiration"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1183\/09031936.02.00253302","article-title":"Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels","volume":"19","author":"Yang","year":"2002","journal-title":"Eur. Respir. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/PL00007570","article-title":"Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in vitro","volume":"175","author":"Gillissen","year":"1997","journal-title":"Lung"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s004330050049","article-title":"Oxidant scavenger function of ambroxol in vitro: A comparison with N-acetylcysteine","volume":"196","author":"Gillissen","year":"1997","journal-title":"Res. Exp. Med. (Berl.)"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10238-006-0099-2","article-title":"Ambroxol for the prevention of acute upper respiratory disease","volume":"6","author":"Nobata","year":"2006","journal-title":"Clin. Exp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/0020-711X(93)90655-X","article-title":"Superoxide radical scavenging activity of phenolic compounds","volume":"25","author":"Tsujimoto","year":"1993","journal-title":"Int. J. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/biof.5520310101","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","volume":"31","author":"Jariwalla","year":"2007","journal-title":"Biofactors"},{"key":"ref_80","first-page":"541","article-title":"Antiviral effects of ascorbic and dehydroascorbic acids in vitro","volume":"22","author":"Furuya","year":"2008","journal-title":"Int. J. Mol. Med."},{"key":"ref_81","first-page":"2413","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","volume":"22","author":"Kimbarowski","year":"1967","journal-title":"Dtsch. Gesundheitsw."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.nut.2009.09.015","article-title":"Combined inhalational and oral supplementation of ascorbic acid may prevent influenza pandemic emergency: A hypothesis","volume":"26","author":"Banerjee","year":"2010","journal-title":"Nutrition"},{"key":"ref_83","first-page":"555","article-title":"Bioactivity of flavonoids","volume":"48","author":"Robak","year":"1996","journal-title":"Pol. J. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/0006-291X(89)92093-7","article-title":"Inhibition of mouse liver sialidase by plant flavonoids","volume":"163","author":"Nagai","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1248\/cpb.38.1329","article-title":"Inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids","volume":"38","author":"Nagai","year":"1990","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0166-3542(92)90080-O","article-title":"In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase","volume":"19","author":"Nagai","year":"1992","journal-title":"Antivir. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1248\/bpb.18.295","article-title":"Antiviral activity of plant flavonoid, 5,7,4\u2019-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis against influenza A (H3N2) and B viruses","volume":"18","author":"Nagai","year":"1995","journal-title":"Biol. Pharm. Bull."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0166-3542(94)00062-D","article-title":"Mode of action of the anti-influenza virus activity of plant flavonoid, 5,7,4\u2019-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis","volume":"26","author":"Nagai","year":"1995","journal-title":"Antivir. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.antiviral.2005.06.010","article-title":"Antiviral effect of catechins in green tea on influenza virus","volume":"68","author":"Song","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1248\/cpb.47.279","article-title":"Effects of catechins on superoxide and hydroxyl radical","volume":"47","author":"Kashima","year":"1999","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1089\/acm.2006.12.669","article-title":"Gargling with tea catechin extracts for the prevention of influenza infection in elderly nursing home residents: A prospective clinical study","volume":"12","author":"Yamada","year":"2006","journal-title":"J. Altern. Complement. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1016\/j.bmcl.2008.02.020","article-title":"Enhanced anti-influenza A virus activity of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives: Effect of alkyl chain length","volume":"18","author":"Mori","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kuzuhara, T., Iwai, Y., Takahashi, H., Hatakeyama, D., and Echigo, N. (2009). Green tea catechins inhibit the endonuclease activity of influenza A virus RNA polymerase. PLoS. Curr., 1.","DOI":"10.1371\/currents.RRN1052"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ejps.2009.03.002","article-title":"Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication","volume":"37","author":"Choi","year":"2009","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.antiviral.2010.08.016","article-title":"Inhibition of influenza virus replication by plant-derived isoquercetin","volume":"88","author":"Kim","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.fct.2006.08.026","article-title":"Evaluation of the safety and toxicity of the oligomerized polyphenol Oligonol","volume":"45","author":"Fujii","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.phymed.2010.03.016","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","volume":"17","author":"Gangehei","year":"2010","journal-title":"Phytomedicine"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/16\/3\/2032\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:34:42Z","timestamp":1770384882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/16\/3\/2032"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,28]]},"references-count":97,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2011,3]]}},"alternative-id":["molecules16032032"],"URL":"https:\/\/doi.org\/10.3390\/molecules16032032","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,28]]}}}