Systems pharmacology-based exploration reveals mechanisms of anti-steatotic effects of Jiang Zhi Granule on non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), which is in parallel with the obesity epidemic, accounts for a large amount of all chronic liver disease. Jiang Zhi Granule (JZG), a clinically used herbal formula, is developed in accordance with traditional Chinese medicine (TCM) pathogenesis for treating patients with NAFLD. In previous studies, the anti-steatotic effects of JZG against NAFLD have been demonstrated, and in this study, a systems pharmacology approach was used to explore the pharmacological mechanisms of JZG by predicting the active compounds within the herbal formula and their corresponding therapeutic targets. Its therapeutic efficacy was confirmed in the beginning of this study, and JZG was shown to significantly improve hepatic dysfunction and lipid droplet accumulation in PA-treated hepatocytes. Systems pharmacology was then performed to identify the active compounds in as well as to predict the therapeutic targets of this Chinese herbal prescription. Enrichment analyses indicated that the mechanisms of the anti-steatotic effects of JZG against NAFLD might be associated with lipid droplet degradation via autophagy, and a series of in vitro and in vivo validation experiments was subsequently performed to confirm that JZG could activate autophagy though the mTOR signalling to improve NAFLD.