Probucol ameliorates hepatic stellate cell activation and autophagy is associated with farnesoid X receptor

Probucol has antioxidant effects and inhibits inflammation. Farnesoid X receptor (FXR) is a nuclear receptor that regulates autophagy, which is regarded as the key cause of the activation of hepatic stellate cell (HSC). In this study, the effects of probucol on HSC activation and autophagy in vitro and vivo and the role of FXR in this progress were investigated. Results showed that probucol ameliorated hepatic fibrosis and autophagy, and increased the expression of FXR in liver in a mouse model of fibrosis induced by CCl4. And probucol could alleviate lipopolysaccharide-induced autophagy and HSC activation in vitro. In addition, probucol increased FXR expression, and the Z-guggulsterone, an antagonist of FXR, could block the effects of probucol on HSC activation and autophagy. Additionally, agonists of FXR could suppress LPS-induced autophagy and activation. These results suggest that probucol could ameliorate hepatic fibrosis, and inhibit HSC autophagy and activation, and these effects are associated with FXR. (c) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).