Dietary daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels

•MicroRNA-122 positively regulates hepatitis C virus replication.•IFN-α is the main antiviral agent of current therapy for hepatitis C.•Daidzein inhibits hepatitis C virus replication by decreasing microRNA-122 levels.•Daidzein enhances the antiviral effect of IFN-α on hepatitis C virus therapy. MicroRNAs are emerging as critical endogenous regulators of gene function. Aberrant regulation of microRNAs is associated with various human diseases, most importantly cancer. MicroRNA-122 (miR-122), a liver-specific microRNA, has been implicated in the control of hepatitis C virus (HCV) RNA replication and its response to interferon (IFN) in human hepatoma cells. Here, we report that daidzein, a naturally occurring plant isoflavone, inhibits HCV replication and enhances the antiviral effect of IFN-α on HCV therapy by decreasing microRNA-122 levels in vitro without significantly affecting cell growth. Moreover, daidzein was found to inhibit the expression of miR-122 and miR-21 by down-regulating the expression of TRBP, indicating that daidzein is possibly a general inhibitor of the miRNA pathway. Thus, daidzein provides new insights for drug discovery and HCV prevention.