Virologica Sinica

, Volume 30, Issue 4, pp 261–268 | Cite as

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

  • Zhikui Cheng
  • Ge Sun
  • Wei Guo
  • Yayun Huang
  • Weihua Sun
  • Fei ZhaoEmail author
  • Kanghong HuEmail author
Research Article


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.


hepatitis B virus (HBV) quercetin flavonol antiviral activity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  2. Baumert TF, Thimme R, von Weizsacker F. 2007. Pathogenesis of hepatitis B virus infection. World J Gastroenterol, 13: 82–90.PubMedCentralCrossRefPubMedGoogle Scholar
  3. Beck J, Nassal M. 2007. Hepatitis B virus replication. World J Gastroenterol, 13: 48–64.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.PubMedGoogle Scholar
  8. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  11. Kaul TN, Middleton E, Jr., Ogra PL. 1985. Antiviral effect of flavonoids on human viruses. J Med Virol, 15: 71–79.CrossRefPubMedGoogle Scholar
  12. Kelly GS. 2011. Quercetin. Monograph. Altern Med Rev, 16: 172–194.PubMedGoogle Scholar
  13. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. Liaw YF. 2009. Natural history of chronic hepatitis B virus infection and long-term outcome under treatment. Liver Int, 29 Suppl 1: 100–107.CrossRefPubMedGoogle Scholar
  17. Liaw YF, Chu CM. 2009. Hepatitis B virus infection. Lancet, 373: 582–592.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.PubMedCentralPubMedGoogle Scholar
  20. Nassal M. 2008. Hepatitis B viruses: reverse transcription a different way. Virus Res, 134: 235–249.CrossRefPubMedGoogle Scholar
  21. Powers MV, Workman P. 2007. Inhibitors of the heat shock response: biology and pharmacology. FEBS Lett, 581: 3758–3769.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. Seeger C, Mason WS. 2000. Hepatitis B virus biology. Microbiol Mol Biol Rev, 64: 51–68.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 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.PubMedCentralPubMedGoogle Scholar
  25. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  26. Trepo C, Chan HL, Lok A. 2014. Hepatitis B virus infection. Lancet.Google Scholar
  27. Urban S, Schulze A, Dandri M, Petersen J. 2010. The replication cycle of hepatitis B virus. J Hepatol, 52: 282–284.CrossRefPubMedGoogle Scholar
  28. 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.PubMedCentralCrossRefPubMedGoogle Scholar
  29. Yang P, Markowitz GJ, Wang XF. 2014. The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma. Natl Sci Rev, 1: 396–412.PubMedCentralCrossRefPubMedGoogle Scholar
  30. Yuen MF, Lai CL. 2001. Treatment of chronic hepatitis B. Lancet Infect Dis, 1: 232–241.CrossRefPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.State Key Laboratory of Virology, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina
  2. 2.Sino-Germany Biomedical CenterHubei University of TechnologyWuhanChina
  3. 3.Department of Infectious Disease and Institute of Infectious Disease, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations