Exploration of the Potential Mechanisms of Anaphalis virgata Extract in Treating Diabetic Hepatic Injury Based on Network Pharmacology and Experimental Validation.

Diabetic hepatic injury is a common complication of diabetes, yet it is often neglected due to its subtle early symptoms. This study explored the effect and mechanism of Anaphalis virgata extract (AVE) in treating diabetic hepatic injury. Serum-exposed components of AVE were identified by LC-MS and used for network pharmacology to predict therapeutic targets and pathways. AVE was evaluated in diabetic rats treated intragastrically at 50, 100, and 200 mg/kg for 10 weeks. Hepatic biochemical parameters were measured, and mechanisms were verified by molecular dynamics (MD) simulation, ELISA, and Western blot. Thirty-one serum-exposed compounds (8 prototypes and 23 metabolites) were identified, primarily flavonoids, phenolic acids, terpenoids, and phenylpropanoids. Network pharmacology revealed pathways including lipid and atherosclerosis, IL-17, and AGE-RAGE signaling. Apigenin, kaempferol, and caffeic acid were identified as core compounds, and IL-6, TNF, and IL-1β as core targets. In vivo, AVE significantly decreased hepatic IL-6, TNF, IL-1β, TC, TG, FFA, AST, and ALT levels in diabetic rats. Western blot showed that AVE up-regulated AKT and AMPK while down-regulating NF-κB and GSK-3β pathways. AVE exerts a therapeutic effect on diabetic hepatic injury through anti-inflammatory mechanisms, providing a foundation for its further development and clinical application.