Chlorogenic acid alleviated liver fibrosis in methionine and choline deficient diet-induced nonalcoholic steatohepatitis in mice and its mechanism

Abstract

Nonalcoholic steatohepatitis, one of the most common chronic liver diseases, is a progressive form of nonalcoholic fatty liver disease accompanied by the development of liver fibrosis. Chlorogenic acid (CGA) is a natural polyphenolic compound. This study aims to observe the CGA-provided alleviation on liver fibrosis in methionine and choline deficient (MCD) diet-induced nonalcoholic steatohepatitis in mice and to elucidate its engaged mechanism. CGA attenuated hepatocellular injury, decreased the elevated hepatic lipids accumulation and attenuated liver fibrosis by reducing hepatic collagen deposition in mice fed with MCD diet. CGA abrogated the activation of hepatic stellate cells (HSCs) and promoted mitochondrial biogenesis both in vivo and in vitro. Moreover, the CGA-provided inhibition on HSCs activation in vitro was obviously disappeared after the application of peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PGC1α) siRNA. CGA reduced the enhanced hepatic extracellular matrix (ECM) expression and the elevated serum high-mobility group box 1 (HMGB1) content in mice fed with MCD diet. CGA decreased the HMGB1-induced ECM production in both human liver sinusoidal endothelial cells and human umbilical vein endothelial cells. CGA also weakly promoted mitochondrial biogenesis in both liver sinusoidal endothelial cells and human umbilical vein endothelial cells incubated with HMGB1. Hence, CGA ameliorated hepatic fibrosis in mice fed with MCD diet through inhibiting HSCs activation via promoting mitochondrial biogenesis and reducing the HMGB1-initiated ECM production in hepatic vascular endothelial cells.