Network pharmacology reveals the multiple mechanisms of Xiaochaihu decoction in the treatment of non-alcoholic fatty liver disease

BACKGROUND: Non-alcoholic fatty liver (NAFLD) is a chronic disease worldwide, which poses a huge threat to human health. Xiaochaihu decoction is a well-known traditional Chinese medicine prescription. It has been proven effective in treating NAFLD but its mechanism is still unclear. OBJECTIVE: Multiple mechanisms of Xiaochaihu decoction are explored by identifying and connecting potential targets and active ingredients in the treatment of NAFLD. METHODS: Active ingredients and related targets of seven herbs were collected from TCMSP database. The related targets of NAFLD were obtained from Genes cards database, TDD and OMIM database. The intersected targets of disease targets and drug targets were input into STRING database to construct protein-protein interaction network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. RESULTS: After screening and removal of duplicates, a total of 145 active ingredients and 105 potential targets were obtained. PPI network manifested that AKT1, IL6, JUN MAPK8 and STAT3 were the key target proteins. The results of GO enrichment analysis mainly involved cytokine receptor binding, cytokine activity, and heme binding. The results of KEGG analysis suggested that the mechanism mainly involved in AGE-RAGE signaling pathway in diabetic complications, Hepatitis C, fluid shear stress and atherosclerosis. The signaling pathways were further integrated as network manner, including AGE-RAGE signaling pathway in diabetic complications, Fluid shear stress and atherosclerosis, Insulin resistance, HIF-1 signaling pathway, Th17 cell differentiation and IL-17 signaling pathway. The network contained immunity regulation, metabolism regulation and oxidative stress regulation. CONCLUSION: Xiaochaihu decoction plays a key role in the treatment of NAFLD with multiple targets and pathways. Immunity regulation, metabolism regulation and oxidative stress regulation consist of the crucial regulation cores in mechanism. GRAPHICAL ABSTRACT: Design and workflow of this study [Image: see text]