Scoparone alleviates inflammation, apoptosis and fibrosis of non-alcoholic steatohepatitis by suppressing the TLR4/NF-κB signaling pathway in mice

Abstract

Scoparone, a naturally-occurring, bioactive compound isolated from the Chinese herb Artemisia capillaria, has been shown to ameliorate hepatotoxicity and cholestasis in liver diseases. However, the pharmacological effect of scoparone in non-alcoholic steatohepatitis (NASH) has not been elucidated. In this study, we investigated the protective effects and mechanisms of scoparone in NASH. In vivo, the NASH model was established in mice fed a methionine and choline-deficient (MCD) diet for 4weeks, with or without simultaneous scoparone treatment. In vitro, RAW264.7 cells induced by lipopolysaccharide (LPS) were pretreated with or without different concentrations of scoparone. Hepatic triglycerides and serum AST and ALT levels were examined by biochemical assays. Hepatic histology was assessed by H&E, oil red O and Masson's trichrome staining methods, which were applied to analyze the protective effects of scoparone in NASH. To further explore the underlying mechanism of scoparone, immunohistochemistry, TUNEL, qRT-PCR, and Western blotting assays were applied to liver tissue or LPS-induced RAW264.7 cells. We found that scoparone can effectively improve hepatic steatosis, apoptosis, inflammation, and fibrosis in an MCD diet-induced NASH murine model. Mechanistically, we demonstrated that scoparone treatment alleviates NASH- and lipopolysaccharide (LPS)-induced immune responses in macrophages partly by blocking TLR-4/NF-κB signaling in a dose-dependent manner. Taken together, our results present the potential protective effects and mechanism of scoparone in NASH, suggesting a potentially beneficial drug treatment for NASH.

Keywords: Apoptosis; Fibrosis; Inflammation; Non-alcoholic steatohepatitis; Scoparone.