Metabolomics study on Hericium erinaceus polysaccharides in intervening ethanol induced gastric ulcer in mice

Based on previous evidence indicating the gastroprotective potential of Hericium erinaceus polysaccharides (HEP), this study aimed to evaluate their protective effects against ethanol-induced gastric ulcers in mice and characterize the associated serum metabolic changes using an untargeted metabolomics approach. Determinations of gastric ulcer severity, biochemical indicators, and serum metabolites in mice showed that intragastric administration of HEP reduced ulcer severity. Serum tests confirmed its regulatory effects on oxidative stress and inflammatory markers. Gastric tissue analysis revealed that HEP modulated mucosal barrier integrity and apoptotic pathways. Untargeted metabolomics analysis demonstrated significant differences in serum metabolites among experimental groups. A total of 11 disrupted metabolic pathways were associated with ulcer induction (UC vs NC). In contrast, in mice treated with HEP (HEPh group vs NC), 4 metabolic pathways were significantly altered, namely one‑carbon metabolism via folate, cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, and glycerophospholipid metabolism. Changes in these pathways were associated with improvements in indicators related to oxidative stress status, inflammatory responses, and gastric mucosal repair. This study is the first to systematically analyze serum metabolite changes following HEP intervention in an ethanol-induced gastric ulcer model. The findings provide metabolomic insights into the potential protective effects of HEP and highlight candidate metabolic pathways for further targeted validation.