Mechanism of Action and Target Detection of Danshen & Hawthorn in the Treatment of Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Virtual Docking Simulation

Using network pharmacology, we identified the active ingredients and potential targets of the “Danshen & Hawthorn” herb pair for treating NAFLD. Disease targets for NAFLD were retrieved from relevant databases, and a “herb-ingredient-target” network was constructed. KEGG pathway analysis revealed that the therapeutic mechanism was associated with the IL-17, TNF, and PPAR signaling pathways, among others. Experimental validation in both in vitro (cellular model of steatosis) and in vivo (zebrafish model of NAFLD) models demonstrated that the herbal extract alleviated high-fat-induced damage. Virtual molecular docking of the top-ranked compound-target pairs identified potential key binding residues: PHE 207, TYR 134, HIS 25, GLY 143, and SER 53 for Pparg-Quercetin; ILE 317, MET 355, and PHE 273 for Ppara-Eburicoic acid; and ILE 354, PHE 351, TYR 314, SER 280, and HIS 440 for Hmox1-Dehydroeburicoic acid. In conclusion, the “Danshen & Hawthorn” herb pair ameliorates NAFLD by modulating the expression of PPARα, TNF-α, and IL-17, thereby reducing inflammation and lipid accumulation. This study provides molecular-level insights by identifying critical amino acid residues for target engagement.