Beneficial effect of resveratrol on α-naphthyl isothiocyanate-induced cholestasis via regulation of the FXR pathway

Abstract

Cholestasis is defined as a functional impairment of bile secretion which results in the accumulation of bile acids (BAs) and other toxic molecules in the blood and liver, however, there are very few effective therapies for cholestasis. The farnesoid X receptor (FXR), as a nuclear receptor for BAs, is important in the regulation of BA levels in enterohepatic circulation. It has previously been demonstrated that activation of the FXR pathway may be a useful strategy with which to treat cholestasis. Resveratrol, one of the important ingredients from grape skins and Chinese medicine Polygonum cuspidatum, resulted in FXR-activated effects in vitro and exhibited a protective effect against a-naphthylisothiocyanate (ANIT)-induced cholestasis through FXR regulation in vivo. The underlying mechanisms of resveratrol against ANIT-induced cholestasis may be due to the regulation of BA homeostasis, improvement of liver injury and attenuation of the inflammatory response, which were regulated in a FXR-dependent manner and in turn contributed to overall cholestasis alleviation. Overall, resveratrol as a FXR agonist may act as a potential compound for the treatment of drug-induced cholestasis.