Shugan Jiangzhi Decoction Alleviates Nonalcoholic Fatty Liver Disease（NAFLD） via Regulating AMPK/PPAR Signaling Pathway

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Shugan Jiangzhi Decoction (SJD), a traditional Chinese medicine (TCM) formula which consists of six Chinese herbs, has been used for treating hyperlipidemia, obesity, and fatty liver in Guangdong Provincial Hospital of Traditional Chinese Medicine for over twenty years. Objective: This study aims to elucidate the chemical basis and the molecular mechanism of SJD against NAFLD. Methods: The main components of SJD were determined by High Performance Liquid Chromatography (HPLC). Then the high-fat diet (HFD)-induced NAFLD rat model was established. After treatment with different doses of SJD, the body weight of rats was measured weekly. On the last day of the experiments, the hepatic morphology, histopathology changes, and the serum lipid levels were detected. Then techniques of network pharmacology were employed to predict the anti-NAFLD mechanism of SJD. At last, the expression levels of proteins were measured by western blot to verify the mechanism. Results: Nine chemical constituents of SJD were identified from HPLC fingerprint spectrum. For the in vivo experiment, NAFLD rat model was constructed successfully by feeding high-fat diet (HFD) for 8 weeks. The following treatment with SJD for 6 weeks decreased the fatty droplet accumulation in the liver obviously. Meanwhile, the serum level of high-density lipoprotein cholesterol (HDL-c) was increased, while the levels of low-density lipoprotein cholesterol (LDL-c), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were decreased after SJD treatment(p<0.05). The results of network pharmacology indicated that SJD might improve NAFLD via regulating the AMPK/PPAR signaling pathway. Then, the western blot assay confirmed that SJD activated the AMPK/PPAR signaling pathway in the liver of rats. Conclusion: SJD improves HFD-induced NAFLD in rats via AMPK/PPAR signaling pathway. Thus, our study suggests that SJD can serve as a therapeutic agent for the prevention and treatment of NAFLD.