Lei Zhu, Yexin Tang, Qinglan Song, Yongbo Wang
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.
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.