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Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines

Virologica Sinica

Abstract

Hepatitis B virus (HBV) infection is one of the most serious and prevalent viral diseases in the world. Although several anti-HBV drugs have been used clinically, their side and adverse effects limit treatment efficacy. Therefore, it is necessary to identify novel potential anti-HBV agents. The flavonol quercetin has shown activity against some retroviruses, but its effect on HBV remains unclear. In the present study, quercetin was incubated with HepG2.2.15 cells, as well as HuH-7 cells transfected with an HBV plasmid. Quercetin was shown to significantly reduce Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg), secretion and HBV genomic DNA levels in both cell lines. In addition, co-incubation with lamivudine (3TC), entecavir (ETV), or adefovir (Ade) further enhanced the quercetin-induced inhibition of HBV replication. This inhibition was partially associated with decreased heat shock proteins and HBV transcription levels. The results indicate that quercetin inhibited HBV antigen secretion and genome replication in human hepatoma cell lines, which suggests that quercetin may be a potentially effective anti-HBV agent.

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References

  • Bader T, Korba B. 2010. Simvastatin potentiates the anti-hepatitis B virus activity of FDA-approved nucleoside analogue inhibitors in vitro. Antiviral Res, 86: 241–245.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Baumert TF, Thimme R, von Weizsacker F. 2007. Pathogenesis of hepatitis B virus infection. World J Gastroenterol, 13: 82–90.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Beck J, Nassal M. 2007. Hepatitis B virus replication. World J Gastroenterol, 13: 48–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Davis JM, Murphy EA, McClellan JL, Carmichael MD, Gangemi JD. 2008. Quercetin reduces susceptibility to influenza infection following stressful exercise. Am J Physiol Regul Integr Comp Physiol, 295: R505–509.

    Article  Google Scholar 

  • Feng H, Chen P, Zhao F, Nassal M, Hu K. 2013. Evidence for multiple distinct interactions between hepatitis B virus P protein and its cognate RNA encapsidation signal during initiation of reverse transcription. PLoS One, 8: e72798.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gonzalez O, Fontanes V, Raychaudhuri S, Loo R, Loo J, Arumugaswami V, Sun R, Dasgupta A, French SW. 2009. The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology, 50: 1756–1764.

    Article  CAS  PubMed  Google Scholar 

  • Gulati N, Laudet B, Zohrabian VM, Murali R, Jhanwar-Uniyal M. 2006. The antiproliferative effect of Quercetin in cancer cells is mediated via inhibition of the PI3K-Akt/PKB pathway. Anticancer Res, 26: 1177–1181.

    CAS  PubMed  Google Scholar 

  • Guo H, Zhou T, Jiang D, Cuconati A, Xiao GH, Block TM, Guo JT. 2007. Regulation of hepatitis B virus replication by the phosphatidylinositol 3-kinase-akt signal transduction pathway. J Virol, 81: 10072–10080.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hakkinen SH, Karenlampi SO, Heinonen IM, Mykkanen HM, Torronen AR. 1999. Content of the flavonols quercetin, myricetin, and kaempferol in 25 edible berries. J Agric Food Chem, 47: 2274–2279.

    Article  CAS  PubMed  Google Scholar 

  • Hu J, Flores D, Toft D, Wang X, Nguyen D. 2004. Requirement of heat shock protein 90 for human hepatitis B virus reverse transcriptase function. J Virol, 78: 13122–13131.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kaul TN, Middleton E, Jr., Ogra PL. 1985. Antiviral effect of flavonoids on human viruses. J Med Virol, 15: 71–79.

    Article  CAS  PubMed  Google Scholar 

  • Kelly GS. 2011. Quercetin. Monograph. Altern Med Rev, 16: 172–194.

    PubMed  Google Scholar 

  • Kumar P, Sharma S, Khanna M, Raj HG. 2003. Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection. Int J Exp Pathol, 84: 127–133.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Larson AJ, Symons JD, Jalili T. 2012. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr, 3: 39–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Levrero M, Pollicino T, Petersen J, Belloni L, Raimondo G, Dandri M. 2009. Control of cccDNA function in hepatitis B virus infection. J Hepatol, 51: 581–592.

    Article  CAS  PubMed  Google Scholar 

  • Liaw YF. 2009. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int, 29 Suppl 1: 100–107.

    Article  PubMed  Google Scholar 

  • Liaw YF, Chu CM. 2009. Hepatitis B virus infection. Lancet, 373: 582–592.

    Article  CAS  PubMed  Google Scholar 

  • Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, et al. 2012. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 380: 2095–2128.

    Article  PubMed  Google Scholar 

  • Nassal M. 1992. The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. J Virol, 66: 4107–4116.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nassal M. 2008. Hepatitis B viruses: reverse transcription a different way. Virus Res, 134: 235–249.

    Article  CAS  PubMed  Google Scholar 

  • Powers MV, Workman P. 2007. Inhibitors of the heat shock response: biology and pharmacology. FEBS Lett, 581: 3758–3769.

    Article  CAS  PubMed  Google Scholar 

  • Romero MR, Efferth T, Serrano MA, Castano B, Macias RI, Briz O, Marin JJ. 2005. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system. Antiviral Res, 68: 75–83.

    Article  CAS  PubMed  Google Scholar 

  • Seeger C, Mason WS. 2000. Hepatitis B virus biology. Microbiol Mol Biol Rev, 64: 51–68.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Seifer M, Hamatake RK, Colonno RJ, Standring DN. 1998. In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob Agents Chemother, 42: 3200–3208.

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sells MA, Chen ML, Acs G. 1987. Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci U S A, 84: 1005–1009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Trepo C, Chan HL, Lok A. 2014. Hepatitis B virus infection. Lancet.

    Google Scholar 

  • Urban S, Schulze A, Dandri M, Petersen J. 2010. The replication cycle of hepatitis B virus. J Hepatol, 52: 282–284.

    Article  PubMed  Google Scholar 

  • Wang YP, Liu F, He HW, Han YX, Peng ZG, Li BW, You XF, Song DQ, Li ZR, Yu LY, Cen S, Hong B, Sun CH, Zhao LX, Kreiswirth B, Perlin D, Shao RG, Jiang JD. 2010. Heat stress cognate 70 host protein as a potential drug target against drug resistance in hepatitis B virus. Antimicrob Agents Chemother, 54: 2070–2077.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yang P, Markowitz GJ, Wang XF. 2014. The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma. Natl Sci Rev, 1: 396–412.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yuen MF, Lai CL. 2001. Treatment of chronic hepatitis B. Lancet Infect Dis, 1: 232–241.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Fei Zhao or Kanghong Hu.

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ORCID: 0000-0001-8044-7889

ORCID: 0000-0003-1393-3734

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Cheng, Z., Sun, G., Guo, W. et al. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines. Virol. Sin. 30, 261–268 (2015). https://doi.org/10.1007/s12250-015-3584-5

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  • DOI: https://doi.org/10.1007/s12250-015-3584-5

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