Exploring the Protective Effect of Xiangsha Yangwei Pills on Alcohol-Induced Gastric Injury Using an Integrated...

Alcohol-induced gastric injury is a common clinical problem with few good preventive options. In this study, we examined whether Xiangsha Yangwei Pills (XS), a traditional herbal formula used for digestive issues, could protect against ethanol-induced gastric damage and sought to elucidate how it might work.

We combined network toxicology and network pharmacology to identify the main active compounds in XS and their potential biological targets. Two key components that emerged from this analysis, quercetin and borneol, were then examined using computational methods to predict their antioxidant activity-specifically their electron-acquisition ability and frontier orbital energy gaps. We also conducted in vitro experiments to directly test how well XS scavenges free radicals and chelates metal ions. For in vivo testing, we used a mouse model of alcohol-induced gastric injury and measured parameters such as gastric mucosal lesion severity, ulcer index scores, and total ulcer area to assess whether XS had a protective effect.

The network analysis identified nineteen central targets, many of which were antioxidant-related enzymes such as superoxide dismutase, catalase, and myeloperoxidase. Our computational results suggested that the main active compounds have strong antioxidant potential, which was supported by the in vitro findings, showing that XS effectively scavenges free radicals and chelates metal ions. In the animal model, administering XS beforehand significantly reduced gastric mucosal damage, reducing both ulcer scores and the affected area by more than 80%. At the molecular level, XS treatment increased the activity of the body's own antioxidant enzymes (superoxide dismutase, catalase) and reduced tissue levels of oxidative stress markers such as malondialdehyde and myeloperoxidase.

The integration of network toxicology and pharmacology revealed 19 overlapping targets, predominantly antioxidant enzymes, suggesting that the gastroprotective effect of XS is mechanistically mediated by mitigating oxidative stress. This computational prediction was empirically validated by the observed increase in superoxide dismutase and catalase activities and the reduction in malondialdehyde and myeloperoxidase levels in vivo. Notably, the high binding affinities of core components such as quercetin and borneol to key targets (e.g., AKT1, TNF, TP53) suggest that XS may exert synergistic, multi-target modulation beyond direct radical scavenging, potentially influencing cell survival and inflammatory pathways. These findings position XS as a promising multi-component strategy for managing alcohol-induced gastric injury, bridging traditional use with modern mechanistic evidence.

Overall, our findings show that XS offers strong protection against alcohol-induced gastric injury. The main mechanism appears to be strengthening the antioxidant defense system in the gastric mucosa. These results provide scientific support for using XS as a potential approach to help reduce alcohol- related gastric damage.