Gastroprotective potential of Dendrobium nobile Lindl. aqueous extract against alcohol-induced gastric mucosal barrier injury: Insights from multi-omics and network pharmacology

Dendrobium nobil e Lindl. (DN) is a widely used herbal medicine in China. Traditionally, it has been commonly consumed as a tea beverage and is believed to possess protective effects on the gastrointestinal tract. This study aimed to investigate the gastroprotective effects and potential correlative networks of a DN aqueous extract against acute alcohol-induced gastric ulcers in rats using histological, biochemical, integrated multi-omics, and network pharmacology approaches. The in vivo administration of DN significantly attenuated macroscopic and microscopic gastric mucosal injury, restored gastric fluid pH, and enhanced mucosal barrier integrity by upregulating the expression of tight junction proteins (ZO-1 and Occludin). Furthermore, DN effectively mitigated oxidative stress (modulating MDA, SOD, and NO levels) and suppressed the excessive secretion of pro-inflammatory cytokines (IL-6, IL-1β, and IFN-γ). 16S rRNA sequencing and metabolomics revealed that the 14-day DN pre-conditioning induced shifts in the gut microbiota—increasing beneficial taxa (Marvinbryantia and HT002 ) and decreasing the genus Gemella —and modulated metabolic profiles, which were strongly associated with enhanced mucosal resilience. Additionally, network pharmacology combined with in vivo validation indicated that these protective effects are closely linked to the activation of the PI3K/Akt signaling pathway. In conclusion, DN alleviates acute alcohol-induced gastric damage primarily by suppressing localized oxidative/inflammatory stress and reinforcing barrier function. Furthermore, its prophylactic efficacy is closely associated with gut microbiota-metabolome axis and PI3K/Akt signaling. These findings scientifically validate the traditional application of DN and highlight its promising potential as a functional food ingrdent.