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Zhikui Cheng, Ge Sun, Wei Guo, Yayun Huang, Weihua Sun, Fei Zhao and Kanghong Hu. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines[J]. Virologica Sinica, 2015, 30(4): 261-268. doi: 10.1007/s12250-015-3584-5
Citation: Zhikui Cheng, Ge Sun, Wei Guo, Yayun Huang, Weihua Sun, Fei Zhao, Kanghong Hu. Inhibition of hepatitis B virus replication by quercetin in human hepatoma cell lines [J].VIROLOGICA SINICA, 2015, 30(4) : 261-268.  http://dx.doi.org/10.1007/s12250-015-3584-5

橡黄素在肝癌细胞系中对乙肝病毒的抑制作用

  • 通讯作者: 赵非, zhaofei@wh.iov.cn, ORCID: 0000-0003-1393-3734
    胡康洪, hukh@mail.hbut.edu.cn, ORCID: 0000-0001-8044-7889
  • 收稿日期: 2015-03-17
    录用日期: 2015-08-03
    出版日期: 2015-08-08
  • 乙型肝炎病毒(HBV)感染是世界范围内最为严重,且传播最为广泛的一种病毒性疾病。虽然已有数种抗乙肝药物在临床中被使用,但它们的局限及副作用限制了其治疗效果,因此寻找新型抗乙肝药物依然十分必要。橡黄素被证实能抑制多种反转录病毒,但它对乙肝的作用依然未知。本研究中,利用橡黄素处理HepG2.2.15细胞和转染乙肝病毒质粒的HuH-7细胞,结果证实其能显著降低乙肝表面抗原(sAg)和e抗原(eAg)的分泌,并下调病毒基因组DNA水平,而与拉米夫定(3TC),恩替卡韦(ETV)或阿德福韦(Ade)共处理会进一步增强它对乙肝病毒的抑制作用,且这些抑制作用被证实与热休克蛋白及病毒转录水平的下降相关。以上说明橡黄素能在肝癌细胞系中有效抑制乙肝病毒的抗原分泌和基因组复制,并具有成为一种抗乙肝药物的潜力。

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

  • Corresponding author: Fei Zhao, zhaofei@wh.iov.cn Kanghong Hu, hukh@mail.hbut.edu.cn
  • ORCID: 0000-0003-1393-3734; 0000-0001-8044-7889
  • Received Date: 17 March 2015
    Accepted Date: 03 August 2015
    Published Date: 08 August 2015
  • 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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    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.
        doi: 10.1016/j.antiviral.2010.02.325

    2. Baumert TF, Thimme R, von Weizsacker F. 2007. Pathogenesis of hepatitis B virus infection. World J Gastroenterol, 13: 82-90.
        doi: 10.3748/wjg.v13.i1.82

    3. Beck J, Nassal M. 2007. Hepatitis B virus replication. World J Gastroenterol, 13: 48-64.
        doi: 10.3748/wjg.v13.i1.48

    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.
        doi: 10.1152/ajpregu.90319.2008

    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.
        doi: 10.1371/journal.pone.0072798

    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.
        doi: 10.1002/hep.23232

    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.

    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.
        doi: 10.1128/JVI.00541-07

    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.
        doi: 10.1021/jf9811065

    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.
        doi: 10.1128/JVI.78.23.13122-13131.2004

    11. Kaul TN, Middleton E, Jr., Ogra PL. 1985. Antiviral effect of flavonoids on human viruses. J Med Virol, 15: 71-79.
        doi: 10.1002/(ISSN)1096-9071

    12. Kelly GS. 2011. Quercetin. Monograph. Altern Med Rev, 16: 172-194.

    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.
        doi: 10.1046/j.1365-2613.2003.00344.x

    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.
        doi: 10.3945/an.111.001271

    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.
        doi: 10.1016/j.jhep.2009.05.022

    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.

    17. Liaw YF, Chu CM. 2009. Hepatitis B virus infection. Lancet, 373: 582-592.
        doi: 10.1016/S0140-6736(09)60207-5

    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.
        doi: 10.1016/S0140-6736(12)61728-0

    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.

    20. Nassal M. 2008. Hepatitis B viruses: reverse transcription a different way. Virus Res, 134: 235-249.
        doi: 10.1016/j.virusres.2007.12.024

    21. Powers MV, Workman P. 2007. Inhibitors of the heat shock response: biology and pharmacology. FEBS Lett, 581: 3758-3769.
        doi: 10.1016/j.febslet.2007.05.040

    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.
        doi: 10.1016/j.antiviral.2005.07.005

    23. Seeger C, Mason WS. 2000. Hepatitis B virus biology. Microbiol Mol Biol Rev, 64: 51-68.
        doi: 10.1128/MMBR.64.1.51-68.2000

    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.

    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.
        doi: 10.1073/pnas.84.4.1005

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

    27. Urban S, Schulze A, Dandri M, Petersen J. 2010. The replication cycle of hepatitis B virus. J Hepatol, 52: 282-284.
        doi: 10.1016/j.jhep.2009.10.031

    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.
        doi: 10.1128/AAC.01764-09

    29. Yang P, Markowitz GJ, Wang XF. 2014. The hepatitis B virus-associated tumor microenvironment in hepatocellular carcinoma. Natl Sci Rev, 1: 396-412.
        doi: 10.1093/nsr/nwu038

    30. Yuen MF, Lai CL. 2001. Treatment of chronic hepatitis B. Lancet Infect Dis, 1: 232-241.
        doi: 10.1016/S1473-3099(01)00118-9

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

      Corresponding author: Fei Zhao, zhaofei@wh.iov.cn
      Corresponding author: Kanghong Hu, hukh@mail.hbut.edu.cn
    • 1. State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    • 2. Sino-Germany Biomedical Center, Hubei University of Technology, Wuhan 430068, China
    • 3. Department of Infectious Disease and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

    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.