OBJECTIVE To preliminarily explore the material basis and mechanism of Wendan decoction (WDD) in the treatment of nonalcoholic fatty liver disease (NAFLD).

METHODS Blood glucose level was monitored by glucometer. HE and Oil red O staining were used to detect liver lesions and lipid deposition in mice. Serum lipid, ALT and AST levels in mice were detected by biochemical immune pipeline. WDD blood-absorbed components were detected by UPLC-Q-TOF-MS/MS. Network pharmacology and molecular docking were used to predict the core targets and potential active ingredients of WDD in the treatment of NAFLD. The expression of CYP7A1, FXR, PPARα and PPARγ, which were key regulatory molecules of bile acid and lipid metabolism, were detected by Western blot.

RESULTS WDD improved insulin resistance, liver tissue lesions and lipid deposition in NAFLD mice, and facilitated the passage of bile from the gallbladder into the intestine through the duodenum. A total of 67 blood-absorbed components were identified from the serum of WDD treated mice, and network pharmacology screened out PPARG, FXR and other core targets regulating lipid and bile acid metabolism, and screened out the top 15 potential active components. Among them, glycyrrhetinic acid and other components had high binding energy with PPARs, which may be candidate components for bidirectional regulation of PPARs by WDD. Western blot results showed that high dose of WDD could reduce CYP7A1 and PPARγ (P<0.01, P<0.001) and increase the expression of FXR and PPARα (P<0.001).

CONCLUSION WDD can effectively improve liver tissue lesions and lipid deposition in NAFLD mice, and regulate bile acid metabolism. Glycyrrhetinic acid and other components have strong PPARs targeting activity, which can be used as candidate components for further exploration.