Protective Effects and Underlying Mechanisms of Isoschaftoside Against Aspirin-Induced Gastric Mucosal Injury in Mice

Background and Objective: The gastric mucosa is crucial for preventing gastric diseases. Isoschaftoside (Is), isolated from Dendrobium huoshanense, has shown a gastroprotective effect in our previous in vitro study. Thus, this study aimed to evaluate the protective role of Is in an in vivo model of aspirin-triggered gastric injury in mice and explore the underlying mechanisms. Methods: A total of 72 male C57BL/6J mice were classified into control, model, omeprazole (OME, 20 mg/kg), and low- (Is-L, 7.8 mg/kg), medium- (Is-M, 31.2 mg/kg), and high-dose isoschaftoside (Is-H, 93.6 mg/kg) groups. In the model group, aspirin (300 mg/kg) was administered orally for 14 days to induce gastric injury. At the end of the trial, blood sample were taken. Gastric tissues were harvested and prepared for histopathological examination and immunohistochemical identification of mucin 2 (MUC2) expression. ELISA was performed to measure serum levels of interleukin (IL)-6/1β, tumor necrosis factor-α (TNF-α), cyclooxygenase-1 (COX-1), and prostaglandin E2 (PGE2) levels were measured by ELISA. Western blot was used o detect B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-9, phospho-phosphatidylinositol 3-kinase (p-PI3K), and phospho-protein kinase B (p-AKT) proteins. Results: Is promoted dose-dependent improvement mucosal structure and reduced inflammation, with high-dose efficacy comparable to that of OME. Furthermore, Is significantly decreased IL-6/1β, and TNF-α levels, increased COX-1 and PGE2, upregulated Bcl-2, downregulated Bax and cleaved-caspase-9, and inhibited PI3K/AKT phosphorylation. Additionally, Is reduced the aspirin-induced upregulation of MUC2 expression, further supporting the role of Is in promoting mucosal repair. Conclusion: Is alleviates aspirin-induced gastric injury by inhibiting inflammation, regulating apoptosis-related proteins, suppressing the PI3K/AKT pathway, and modulating mucin expression, supporting the potential of using Is as a gastric mucosal protective agent.