Multi-Modal Gastroprotective Effects of Dioscin in an Indomethacin-Induced Gastric Ulcer Model: Inflammation, Oxidative Stress, Nitric Oxide Pathways, Apoptosis, and Autophagy

Dioscin has shown protective effects in hepatic, renal, and pulmonary injury models. However, its multi-modal protective profile in NSAID-induced gastric ulceration has not been comprehensively evaluated. We investigated the gastroprotective effects of dioscin at two doses in a gastric ulcer model through biochemical, histopathological, and immunohistochemical alterations. 48 female Wistar albino rats were randomized into six groups: control, vehicle, omeprazole (30 mg/kg), indomethacin (30 mg/kg), dioscin 15 (15 mg/kg) and dioscin 30 (30 mg/kg). Blood and gastric tissues were collected 4 h after ulcer induction. IL-1β, TNF-α, IL-10, SOD, MDA, IMA, iNOS, and eNOS levels were measured by ELISA. Gastric lesions were graded histologically. Immunohistochemistry was performed for Bcl-2, p-Caspase-3, p-LC3B, and p-NFκB p65. Data were analyzed via one-way ANOVA (p < 0.05). Indomethacin markedly increased IL-1β, TNF-α, MDA, IMA, and iNOS while reducing SOD and disrupting mucosal architecture. 15 mg/kg dose of Dioscin produced the strongest suppression of IL-1β and TNF-α and reduced iNOS levels, while the 30 mg/kg dose of Dioscin maximally enhanced SOD activity and increased eNOS expression, indicating improved mucosal perfusion. Histopathology demonstrated dose-responsive restoration of epithelial integrity, with Dioscin (30 mg/kg) group exhibiting near-normal mucosal morphology comparable to omeprazole. Immunohistochemically, Dioscin increased Bcl-2 expression while reducing p-Caspase-3, p-LC3B, and p-NFκB p65, demonstrating amelioration of apoptosis, autophagy activation, and inflammatory signaling. Dioscin confers robust gastroprotection through coordinated anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-modulating mechanisms. The 15 mg/kg dose predominantly attenuates inflammatory responses, whereas the 30 mg/kg dose provides additional mucosal repair via enhanced antioxidant activity and eNOS upregulation.