Network pharmacology-based investigation of the pharmacological mechanisms of diosgenin in nonalcoholic steatohepatitis.

The prevalence of nonalcoholic steatohepatitis (NASH) is rising annually, posing health and economic challenges, with limited treatments available. Diosgenin, a natural steroidal compound found in various plants, holds potential as a therapeutic candidate. Recent studies have confirmed diosgenin's anti-inflammatory and metabolism-modulating properties. However, its therapeutic effects on NASH and the underlying mechanisms are still unclear. This study aims to explore diosgenin's protective effects and pharmacological mechanisms against NASH using network pharmacology, molecular docking, and experimental validation. We gathered potential targets of diosgenin and NASH from various databases to generate protein-protein interaction (PPI) networks. GO and KEGG pathway enrichment analyses identified key targets and mechanisms. Molecular docking confirmed the binding capacity between diosgenin and core target proteins. Additionally, a NASH cell model was developed to validate the pharmacological effects of diosgenin. Our investigation identified nine key targets (ALB, AKT1, TP53, VEGFA, MAPK3, EGFR, STAT3, CASP3, IGF1) that interact with diosgenin. Molecular docking indicated potential bindings interactions, while enrichment analyses revealed that diosgenin may enhance fatty acid metabolism via the PI3K-Akt pathway. Cellular experiments confirmed that diosgenin activates this pathway, reduces SCD1 expression, and decreases triglyceride and IL-6 levels. Our study elucidates that diosgenin may ameliorate triglyceride deposition and inflammation through the PI3K-Akt pathway.