Spinosin Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury by Modulating Oxidative Stress, Inflammation, Apoptosis, and Nrf2/HO-1-Associated Responses

Background/Objectives: Spinosin, a flavone glycoside derived from medicinal plants, has been widely studied for its neuroactive properties; however, its effects on gastric injury remain unclear. Therefore, this study investigated the potential protective role of spinosin against HCl/ethanol-induced gastric lesions and its association with Nrf2/HO-1-related antioxidant responses. Methods: Gastric ulceration was experimentally induced in male Swiss albino mice by intragastric administration of 0.3 M HCl in 70% ethanol. Spinosin was administered orally at doses of 10 and 20 mg/kg, while omeprazole (20 mg/kg) was used as a reference treatment. Results: HCl/ethanol exposure led to pronounced oxidative stress and inflammatory responses, as reflected by increased levels of MDA, NFκB, IL-6, TNF-α, Cox-2, iNOS, IL-1β, Bax, and Cas-3, along with reduced antioxidant enzyme activities (GSH, SOD, CAT), decreased PGE2 and NO levels, and downregulation of Nrf2, HO-1, and Bcl-2 expression. Spinosin administration significantly attenuated gastric injury, suppressed pro-inflammatory mediators, reduced markers of lipid peroxidation and apoptosis, and enhanced antioxidant defenses. In parallel, spinosin treatment was associated with increased expression of Nrf2, HO-1, and Bcl-2. Conclusions: These findings suggest that spinosin mitigates gastric damage and is associated with attenuation of oxidative stress, inflammatory responses, and apoptosis, suggesting a possible contribution of Nrf2/HO-1-related antioxidant responses.