Catalpol prevents alteration of cholesterol homeostasis in non-alcoholic fatty liver disease via attenuating endoplasmic reticulum stress and NOX4 over-expression

Catalpol is a natural product isolated from the root of Rehmannia glutinosa , and contributes to multiple pharmacological functions. Here, we showed the protective effects of catalpol against the alteration of cholesterol homeostasis in non-alcoholic fatty liver disease (NAFLD), and further investigated the role of endoplasmic reticulum stress (ER stress) and NOX4-mediated inhibition in alteration of cholesterol homeostasis by catalpol in NAFLD. NAFLD was induced in vivo in C57BL/6J mice by feeding with high-fat diet (HFD) for 12 weeks or in vitro in HepG2 cells by stimulating with palmitate (PA) for 24 hours. The results showed that catalpol reduced hepatic lipid accumulation, ER stress, NOX4-mediated oxidative stress and alteration of cholesterol homeostasis in HFD-induced C57BL/6J mice and PA-induced HepG2 cells. In addition, NOX4 over-expression was reduced by ER stress inhibitor TUDCA and GRP78 over-expression was down-regulated by NOX4 inhibitor DPI in PA-induced HepG2 cells. The results demonstrated that ER stress and NOX4 over-expression regulated each other in PA-induced NAFLD. Furthermore, administrating with ER stress inhibitor or NOX4 inhibitor attenuated lipid accumulation and alteration of cholesterol homeostasis in NAFLD induced by PA. Therefore, catalpol conferred prevention against alteration of cholesterol homeostasis in NAFLD at least partly through attenuating both ER stress and NOX4 over-expression. Catalpol has protective effects against hepatic lipid accumulation and alteration of cholesterol homeostasis in HFD- and PA-induced NAFLD via inhibiting ER stress and NOX4 over-expression.