D-Mannose Attenuates Ethanol-Induced Gastric Ulcers via Antioxidant Activity Through the HSP90/Nrf2/HO-1 Pathway

Purpose: Gastric ulcer (GU) is a prevalent digestive system disease, yet effective treatment methods remain limited. D-mannose, a monosaccharide isolated from Bletilla striata polysaccharides, has been demonstrated to exhibit significant antioxidant potential in previous studies. Prior investigations have not addressed the therapeutic implications of this compound in preventing alcohol-induced gastric epithelial disruptions. This scientific inquiry is designed to investigate the gastroprotective attributes and antioxidant activity of D-mannose in mitigating alcohol-related gastric ulceration. Methods: An ethanol-induced GU mouse model was established using absolute ethanol. The protective effects and antioxidant activity of different doses of D-mannose (40%, 20% w/v) on gastric tissues were evaluated through morphological observation, pathological staining, and biochemical analysis. Complementarily, computational methodologies encompassing network pharmacological analysis and molecular interaction modeling were utilized to anticipate potential therapeutic mechanisms of D-mannose in gastric ulcer management, subsequently validated through comprehensive experimental investigations in biological systems. Results: D-mannose significantly reduced the ulcer index and pathological scores in gastric tissues, alleviating the damage induced by absolute ethanol. D-mannose markedly increased the activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), while reducing the production of reactive oxygen species (ROS) and malondialdehyde (MDA), thereby enhancing the antioxidant capacity of gastric tissues. Bioinformatics predictions identified HSP90 as the key target for the therapeutic effect of D-mannose on GU. Molecular biology experiments confirmed that D-mannose significantly activated the expression of HSP90 and the downstream Nrf2/HO-1 pathway-related genes and proteins. Similarly, in vitro experiments demonstrated that D-mannose activated key genes and proteins in the HSP90/Nrf2/HO-1 pathway, counteracting oxidative stress damage to gastric epithelial cells induced by absolute ethanol. Conclusion: D-mannose enhances the antioxidant capacity of gastric tissues by activating key molecules in the HSP90/Nrf2/HO-1 pathway, thereby exerting a protective effect on the stomach.