Geniposide Demonstrates Anti-Inflammatory and Antiviral Activity against Pandemic A/Jiangsu/1/2009 (H1N1) Influenza virus Infection in vitro and in vivo

Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team, Dawood FS, Jain S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360: 2605–2615.

Worobey M. , Han G.Z. , Rambaut A. Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc Natl Acad Sci U S A 2014; 111: 8107–8112.

Joseph U. , Linster M. , Suzuki Y. Adaptation of pandemic H2N2 influenza A viruses in humans. J Virol 2015; 89: 2442–2447.

Wendel I. , Rubbenstroth D. , Doedt J. The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus. J Virol 2015; 89: 4170–4179.

Zhou Z. , Li X. , Liu J. Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Res 2015; 25: 39–49.

Gavett S.H. , Haykal-Coates N. , Highfill J.W. World Trade Center fine particulate matter causes respiratory tract hyperresponsiveness in mice. Environ Health Perspect 2003; 111: 981–991.

Sun Y.F. , Wang X.H. , Li X.L. Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China. Vet Microbiol 2016; 183: 85–91.

Zhao G. , Fan Q. , Zhong L. Isolation and phylogenetic analysis of pandemic H1N1/09 influenza virus from swine in Jiangsu province of China. Res Vet Sci 2012; 93: 125–132.

Williams S. , Fitzner J. , Merianos A. The challenges of global case reporting during pandemic A(H1N1) 2009. Bull World Health Organ 2014; 92: 60–67.

Bantia S. , Kellogg D. , Parker C. , Upshaw R. , Ilyushina N.A. , Babu Y.S. A single intramuscular injection of neuraminidase inhibitor peramivir demonstrates antiviral activity against novel pandemic A/California/04/2009 (H1N1) influenza virus infection in mice. Antiviral Res 2011; 90: 17–21.

Takashita E. , Ejima M. , Itoh R. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan, November to December 2013. Euro Surveill 2014; 19: 1–6.

Yu Z. , Cheng K. , Sun W. A PB1 T296R substitution enhance polymerase activity and confer a virulent phenotype to a 2009 pandemic H1N1 influenza virus in mice. Virology 2015; 486: 180–186.

Song X. , Zhang W. , Wang T. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation 2014; 37: 1588–1598.

Deng Y. , Guan M. , Xie X. Geniposide inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. Int Immunopharmacol 2013; 17: 561–567.

Yang Q. , Wu B. , Shi Y. Bioactivity-guided fractionation and analysis of compounds with anti-influenza virus activity from Gardenia jasminoides Ellis. Arch Pharm Res 2012; 35: 9–17.

Shoda J. , Miura T. , Utsunomiya H. Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver. Hepatology 2004; 39: 167–178.

Huang W. , Zhang J. , Moore D.D. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004; 113: 137–143.

Chen J. , Sun M. , Wang X. The herbal compound geniposide rescues formaldehyde-induced apoptosis in N2a neuroblastoma cells. Sci China Life Sci 2014; 57: 412–421.

Kim S.J. , Kim J.K. , Lee D.U. , Kwak J.H. , Lee S.M. Genipin protects lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice. Eur J Pharmacol 2010; 635: 188–193.

Inao M. , Mochida S. , Matsui A. Japanese herbal medicine Inchin-ko-to as a therapeutic drug for liver fibrosis. J Hepatol 2004; 41: 584–591.

Sakaida I. , Tsuchiya M. , Kawaguchi K. , Kimura T. , Terai S. , Okita K. Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient l-amino acid-defined diet. J Hepatol 2003; 38: 762–769.

Sung Y.Y. , Lee A.Y. , Kim H.K. The Gardenia jasminoides extract and its constituent, geniposide, elicit anti-allergic effects on atopic dermatitis by inhibiting histamine in vitro and in vivo. J Ethnopharmacol 2014; 156: 33–40.

Gong N. , Fan H. , Ma A.N. , Xiao Q. , Wang Y.X. Geniposide and its iridoid analogs exhibit antinociception by acting at the spinal GLP-1 receptors. Neuropharmacology 2014; 84: 31–45.

Pan L. , Wang W. , Shi F. Exploratory pharmacokinetics of geniposide in rat model of cerebral ischemia orally administered with or without baicalin and/or berberine. Evid Based Complement Alternat Med 2013; 2013: 349531.

Chen Y.S. , Chang J.Y. , Cheng C.Y. , Tsai F.J. , Yao C.H. , Liu B.S. An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material. Biomaterials 2005; 26: 3911–3918.

Qi X. , Qian Y.H. , Bao C.J. Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation. BMJ 2013; 347: f4752.

Kitano M. , Itoh Y. , Ishigaki H. Efficacy of repeated intravenous administration of peramivir against highly pathogenic avian influenza A (H5N1) virus in cynomolgus macaques. Antimicrob Agents Chemother 2014; 58: 4795–4803.

Tarbet E.B. , Vollmer A.H. , Hurst B.L. , Barnard D.L. , Furuta Y. , Smee D.F. In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus. Arch Virol 2014; 159: 1279–1291.

Yershov A.L. , Jordan B.S. , Guymon C.H. , Dubick M.A. Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model. Eur Respir J 2005; 25: 693–700.

Michaelis M. , Geiler J. , Naczk P. Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced pro-inflammatory cytokine and chemokine expression in human macrophages. Med Microbiol Immunol (Berl) 2010; 199: 291–297.

Triana-Baltzer G.B. , Gubareva L.V. , Nicholls J.M. Novel pandemic influenza A(H1N1) viruses are potently inhibited by DAS181, a sialidase fusion protein. PLoS One 2009; 4: e7788.

Khalili I. , Ghadimipour R. , Sadigh E.S. Evaluation of immune response against inactivated avian influenza (H9N2) vaccine, by using chitosan nanoparticles. Jundishapur J Microbiol 2015; 8: e27035.

Zhu Z. , Yang Y. , Feng Y. Infection of inbred BALB/c and C57BL/6 and outbred Institute of Cancer Research mice with the emerging H7N9 avian influenza virus. Emerg Microbes Infect 2013; 2: e50.

Farooqui A. , Huang L. , Wu S. Assessment of antiviral properties of peramivir against H7N9 avian influenza virus in an experimental mouse model. Antimicrob Agents Chemother 2015; 59: 7255–7264.

Lin Y.J. , Lai C.C. , Lai C.H. Inhibition of enterovirus 71 infections and viral IRES activity by Fructus gardeniae and geniposide. Eur J Med Chem 2013; 62: 206–213.

Mogensen T.H. , Paludan S.R. Molecular pathways in virus-induced cytokine production. Microbiol Mol Biol Rev 2001; 65: 131–150.

Song X. , Zhang W. , Wang T. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation 2014; 37: 1588–1598.

Zhang G. , He J.L. , Xie X.Y. , Yu C. LPS-induced iNOS expression in N9 microglial cells is suppressed by geniposide via ERK, p38 and nuclear factor-kappaB signaling pathways. Int J Mol Med 2012; 30: 561–568.

Sakabe S. , Iwatsuki-Horimoto K. , Takano R. Cytokine production by primary human macrophages infected with highly pathogenic H5N1 or pandemic H1N1 2009 influenza viruses. J Gen Virol 2011; 92: 1428–1434.

Tadokera R. , Meintjes G. , Skolimowska K.H. Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. Eur Respir J 2011; 37: 1248–1259.

Marti L. , Cervera C. , Filella X. , Marin J.L. , Almela M. , Moreno A. Cytokine-release patterns in elderly patients with systemic inflammatory response syndrome. Gerontology 2007; 53: 239–244.

Kaya S. , Elaldi N. , Kubar A. Sequential determination of serum viral titers, virus-specific IgG antibodies, and TNF-alpha, IL-6, IL-10, and IFN-gamma levels in patients with Crimean-Congo hemorrhagic fever. BMC Infect Dis 2014; 14: 416–423.

Wurzer W.J. , Ehrhardt C. , Pleschka S. NF-kappaB-dependent induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas/FasL is crucial for efficient influenza virus propagation. J Biol Chem 2004; 279: 30931–30937.

Wurzer W.J. , Planz O. , Ehrhardt C. Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J 2003; 22: 2717–2728.

Herold S. , Ludwig S. , Pleschka S. , Wolff T. Apoptosis signaling in influenza virus propagation, innate host defense, and lung injury. J Leukoc Biol 2012; 92: 75–82.

Jiang Y.Q. , Chang G.L. , Wang Y. , Zhang D.Y. , Cao L. , Liu J. Geniposide prevents hypoxia/reoxygenation-induced apoptosis in H9c2 Cells: improvement of mitochondrial dysfunction and activation of GLP-1R and the PI3K/AKT signaling pathway. Cell Physiol Biochem 2016; 39: 407–421.

Chen Y. , Zhang Y. , Li L. , Holscher C. Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's disease. Eur J Pharmacol 2015; 768: 21–27.

Xiaofeng Y. , Qinren C. , Jingping H. Geniposide, an iridoid glucoside derived from Gardenia jasminoides, protects against lipopolysaccharide-induced acute lung injury in mice. Planta Med 2012; 78: 557–564.

Jiang S. , Wang Z. , Ouyang H. , Liu Z. , Li L. , Shi Y. Aberrant expression of cytokine interleukin 9 along with interleukin 4 and interferon gamma in connective tissue disease-associated interstitial lung disease: association with severity of pulmonary fibrosis. Arch Med Sci 2016; 12: 101–106.

Sun K. , Salmon S. , Yajjala V.K. , Bauer C. , Metzger D.W. Expression of suppressor of cytokine signaling 1 (SOCS1) impairs viral clearance and exacerbates lung injury during influenza infection. PLOS 2014; 10: 1–11.

Ma T.T. , Li X.F. , Li W.X. Geniposide alleviates inflammation by suppressing MeCP2 in mice with carbon tetrachloride-induced acute liver injury and LPS-treated THP-1 cells. Int Immunopharmacol 2015; 29: 739–747.

Kwit K. , Pomorska-Mól M. , Markowska-Daniel I. Pregnancy outcome and clinical status of gilts following experimental infection by H1N2, H3N2 and H1N1pdm09 influenza A viruses during the last month of gestation. Arch Virol 2015; 160: 2415–2425.

Lv J. , Wang D. , Hua Y.H. Pulmonary immune responses to 2009 pandemic influenza A (H1N1) virus in mice. BMC Infect Dis 2014; 14: 197.

Pomorska-Mol M. , Markowska-Daniel I. , Kwit K. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus. Arch Virol 2014; 159: 2605–2614.

Baurakiades E. , Costa V.H.J. , Raboni S.M. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia. J Clin Virol 2014; 61: 585–589.

Kulkarni U. , Karsten C.M. , Kohler T. IL-10 mediates plasmacytosis-associated immunodeficiency by inhibiting complement-mediated neutrophil migration. J Allergy Clin Immunol 2016; 137: 1487–1497.

Moran T.M. , Isobe H. , Fernandez-Sesma A. , Schulman J.L. Interleukin-4 causes delayed virus clearance in influenza virus-infected mice. J Virol 1996; 70: 5230–5235.

Sun J. , Madan R. , Karp C.L. , Braciale T.J. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 2009; 15: 277–284.

Arriaga-Pizano L. , Ferat-Osorio E. , Rodriguez-Abrego G. Differential immune profiles in two pandemic influenza A(H1N1)pdm09 virus waves at pandemic epicenter. Arch Med Res 2015; 46: 651–658.

Dai M.M. , Wu H. , Li H. Effects and mechanisms of geniposide on rats with adjuvant arthritis. Int Immunopharmacol 2014; 20: 46–53.

Chen J.Y. , Wu H. , Li H. , Hu S.L. , Dai M.M. , Chen J. Anti-inflammatory effects and pharmacokinetics study of geniposide on rats with adjuvant arthritis. Int Immunopharmacol 2015; 24: 102–109.

Wei J. , Zhang F. , Zhang Y. Proteomic investigation of signatures for geniposide-induced hepatotoxicity. J Proteome Res 2014; 13: 5724–5733.

Fu Y. , Liu B. , Liu J. Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models. Int Immunopharmacol 2012; 14: 792–798.