Cangju Qinggan Jiangzhi Decoction Reduces the Development of NonAlcoholic Steatohepatitis and Activation of Kupffer Cells

Abstract

Background/Aims: Nonalcoholic steatohepatitis (NASH) is defined as lipid accumulation with hepatic injury, inflammation and early to moderate fibrosis. Kupffer cells play a crucial role in promoting hepatic inflammation, which further facilitates the development of NASH. Here we investigated the effects of Cangju Qinggan Jiangzhi decoction (CQJD) on high fat diet (HFD) and methionine-choline deficient (MCD) induced mouse NASH pathogenesis. Methods: Mouse NASH models were developed by HFD and MCD diet. The treated mice were divided into three groups: the control group (n = 10), the low-dose CQJD treatment group (n = 10) and the high-dose CQJD treatment group (n = 10). The hepatic injury, inflammation, and apoptotic molecules were evaluated by H&E staining, immunohistochemistry and real-time PCR. Kupffer cells were isolated from control mice and CQJD-treated mice after stimulation by lipopolysaccharide (LPS) and/or palmitic acid. The level of the inflammatory cytokines TNFα, IL1β, and CCL2 was measured by ELISA. Results: The HFD-fed mice displayed significant metabolic, inflammatory, and oxidative stress-related alterations due to hepatic lipid accumulation. CQJD treatment largely normalized the hepatic injury, lowered the ALT/AST level, and reduced the severity of liver inflammation, as revealed by the decreased inflammatory cytokines levels. In vitro, CQJD blocked the activation of LPS- or palmitic acid-primed Kupffer cells in a dose-dependent manner. In the MCD diet-induced NASH mice, similar therapeutic effects of CQJD were also observed. Conclusion: CQJD ameliorates mouse nonalcoholic steatohepatitis. The reduction in liver injury and inflammation induced by CQJD is associated with reduced activation of Kupffer cells. Our results suggest that CQJD is a promising therapeutic strategy in clinical steatohepatitis.