Therapeutic options for ethanol-induced gastric mucosal injury remain limited. To provide new drug options, this study investigated the protective mechanisms of Escin—a compound known for its anti-inflammatory and anti-edematous properties—against this condition, which are currently unreported.

Male SD rats were divided into Control, Ethanol, Escin, and Omeprazole groups. Gastric ulcer index and histopathological scores were compared. Network pharmacology predicted Escin targets. Apoptosis proteins, NF-κB inflammatory pathway proteins, inflammatory factors, and related mRNA expression were analyzed. An Ethanol-induced GES-1 cell injury model was established to evaluate the protective effect of Escin. Genes positively regulating the TNF-α/NF-κB signaling pathway were identified through transcriptome sequencing and validated.

The study found that Escin significantly alleviated the damage of Ethanol to gastric mucosal tissue. Network pharmacology predicted that Escin was closely related to inflammation-related pathways such as NF-κB in the action of gastric ulcers. Escin significantly mitigated ethanol-induced damage by restoring MUC5AC, TFF2, Occludin, suppressing NF-κB activation, downregulating IL-1β, IL-6, and TNF-α at both protein and mRNA levels, and modulating apoptosis by inhibiting Bax/Caspase-3 while promoting Bcl-2 expression Escin's protection against ethanol-induced injury was further validated in cell proliferation assays. Finally, Transcriptomics revealed 27 inflammation-related genes upregulated by ethanol, of which 9 genes including Birc3, Bcl3, SOCS1, SOCS3, CCL2, CX3CL1, Pim1, SGK1, and OSMR positively regulated the TNF-α/NF-κB signaling pathway. Western blot confirmed seven of these are modulated by Escin during its protective action.

The study found that Escin significantly alleviated the damage of Ethanol to gastric mucosal tissue. Network pharmacology predicted that Escin was closely related to inflammation-related pathways such as NF-κB in the action of gastric ulcers. Escin significantly mitigated ethanol-induced damage by restoring MUC5AC, TFF2, Occludin, suppressing NF-κB activation, downregulating IL-1β, IL-6, and TNF-α at both protein and mRNA levels, and modulating apoptosis by inhibiting Bax/Caspase-3 while promoting Bcl-2 expression Escin's protection against ethanol-induced injury was further validated in cell proliferation assays. Finally, Transcriptomics revealed 27 inflammation-related genes upregulated by ethanol, of which 9 genes including Birc3, Bcl3, SOCS1, SOCS3, CCL2, CX3CL1, Pim1, SGK1, and OSMR positively regulated the TNF-α/NF-κB signaling pathway. Western blot confirmed seven of these are modulated by Escin during its protective action.