Polydatin ameliorates alcohol-induced gastric ulcer by inhibiting CASP3-mediated apoptosis.

Objective

To explore the protection of polydatin (PD) against alcoholic gastric ulcer (AIGU) in mice and the related molecular pathways.

Methods

PD targets related to AIGU were predicted using network pharmacology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. A mouse gastric ulcer model was established via intragastric administration of ethanol, and the effects of PD on gastric mucosal morphology, oxidative damage, inflammation, and apoptosis-related proteins were evaluated; In vitro, the effects of PD on ethanol-injured GES-1 cells were further assessed in the presence or absence of the caspase-3 inhibitor Z-DEVD-FMK.

Results

Network pharmacology showed that PD exerts its effects through apoptosis-related pathways. In vivo, PD significantly alleviated gastric mucosal injury, reduced the levels of malondialdehyde and pro-inflammatory cytokines, and increased the activities of antioxidant enzymes. It up-regulated mucosal protection factors (epidermal growth factor, prostaglandin E2) and regulates apoptosis-related proteins (B-cell lymphoma-2, B-cell lymphoma-2-associated X protein, cysteinyl aspartate-specific proteinase-3). In vitro, PD protects gastric mucosal epithelial cells from apoptosis; the caspase-3 inhibitor Z-DEVD-FMK alone mimicked the protective effects of PD, and combined treatment with PD and Z-DEVD-FMK did not produce a markedly additive effect, suggesting that PD exerts its anti-apoptotic effect primarily through inhibition of caspase-3 (CASP3)-mediated apoptosis.

Conclusion

PD exerts antioxidant, anti-inflammatory, and anti-apoptotic effects against AIGU, especially inhibiting CASP3-mediated apoptosis, which shows its potential as a natural gastric protection therapy.