Silybin protects against ethanol-induced acute gastric ulcer in rats with PI3K/AKT-associated phosphorylation changes

This study evaluated the effects of silybin in a rat model of ethanol-induced acute gastric ulcer (AGU) using network pharmacology-guided pathway prioritization, molecular docking, and in vivo validation. Network pharmacology identified 48 computational candidate targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment mapped these targets to 20 pathways, and PI3K/AKT signaling was selected for experimental assessment. Docking analysis indicated that silybin could be accommodated in the selected PI3K and AKT binding pockets. In rats, oral silybin pretreatment reduced macroscopic ulceration and attenuated histological and ultrastructural injury after ethanol challenge. Silybin-treated rats also showed higher VEGF expression, lower iNOS expression, and increased p-PI3K/PI3K and p-AKT/AKT ratios. These results identify PI3K/AKT phosphorylation as a pathway-associated readout accompanying silybin-mediated gastroprotection.