The Effects And Mechanism Of Resveratrol On HBV Replication

BackgroundNowadays the population of chronic hepatitis B combined with a number of metabolic disorders such as diabetes, hepatic steatosis or hypertension, is increasing significantly. Resveratrol (RSV) has been used as a potential preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown.MethodsIn this study, the HBV-expressing hepatocelluar carcinoma cell line HepG2.2.15 and mouse model created by hydrodynamic injection of viral DNA via tail vein were used to detect the effects of RSV on the expression of HBV DNA, RNA, core promoter activity and viral proteins.ResultsWe found that RSV activates HBV core promoter in vitro and in vivo, up-regulates HBV transcription and dramatically enhances HBV DNA replication. This action of RSV is dependent on the activation of fatty acid oxidation-associated transcription factor PPARa/RXRa. Further study reveals that the PPARa/RXRa activation by RSV is mainly mediated through Sirtl/PGC-la pathway. In addition, we found that fatty acid oxidation-associated PPARa activation is also required for the fasting-induced HBV transcription in the mouse model of hepatitis B,ConclusionTaken together, this study identifies that RSV enhances HBV transcription and replication through Sirt1-PGC-1α-PPARα pathway. Patients with chronic hepatitis B infection should be cautious taking RSV as a dietary supplement.