OBJECTIVE To explore the active ingredients, targets, and potential mechanisms of Xiaochaihu Decoction(XCHD) in the treatment of non-alcoholic fatty liver disease (NAFLD) based on the zebrafish model and network pharmacology technology.

METHODS The zebrafish NAFLD model was established by feeding zebrafish larvae with high-fat and high-cholesterol diet. The evaluation indicators, including zebrafish liver phenotype, HE pathological slices, and expression levels of inflammatory factors, were used to comprehensively evaluate the effect of XCHD on NAFLD. Network pharmacology analysis was used to explore its potential mechanisms of action.

RESULTS Compared with the model group, XCHD could dose-dependently reduce the increase of body weight and body mass index of zebrafish larvae model with NAFLD, alleviate liver steatosis, lipid deposition, and structural damage, reduce the levels of TG, TC, ALT, AST in zebrafish, decrease ROS levels, and increase SOD enzyme activity. It also reduced the mRNA expression levels of inflammatory factors TNF-α, IL-6, IL-1β in zebrafish. There were 198 active ingredients and 108 targets of XCHD identified by network pharmacology, mainly enriched in the PI3K-Akt signaling pathway and apoptosis-related signaling pathways. PPI network analysis revealed key active ingredients such as baicalin, 6-gingerol, and core targets such as PTGS2. High-dose XCHD significantly regulated the mRNA expression levels of these core targets in NAFLD zebrafish.

CONCLUSION XCHD can intervene in the early progression of NAFL to NASH through multiple components, pathways, and targets. Its main active ingredient, baicalin, can exert lipid-lowering, hepatoprotective, antioxidant, and anti-inflammatory effects by modulating targets such as PTGS2 and AKT1, and participating in the regulation of the PI3K-Akt signaling pathway and apoptosis-related signaling pathways.