Article Publish Status: FREE
Abstract Title:

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

Abstract Source:

World J Gastroenterol. 2017 Sep 14 ;23(34):6252-6260. PMID: 28974891

Abstract Author(s):

Zhi-Qiang Wei, Yong-Hong Zhang, Chang-Zheng Ke, Hong-Xia Chen, Pan Ren, Yu-Lin He, Pei Hu, De-Qiang Ma, Jie Luo, Zhong-Ji Meng

Article Affiliation:

Zhi-Qiang Wei


AIM: To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism.

METHODS: A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin.

RESULTS: Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20μmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% (P<0.01) and 75.5% (P<0.01), respectively, compared with levels in non-treated cells. Meanwhile, time- and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin.

CONCLUSION: Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

Study Type : In Vitro Study

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Sayer Ji
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