Gastroprotective and antioxidant effects of stachydrine against indomethacin-induced gastric injury via ERK, AKT and iNOS signaling pathways

Stachydrine, a major bioactive alkaloid extracted from Leonurus heterophyllus, is a key component of traditional herbal medicine, recognized for its anti-inflammatory and antioxidant properties. In this study, we investigated the gastroprotective effects of stachydrine and its underlying mechanisms in a mouse model of indomethacin (IND)-induced gastric injury. Mice were intragastrically administered IND at a dose of 40 mg/kg, followed 30 min later by treatment with varying doses of stachydrine (0, 5, and 10 mg/kg). Six hours post-IND administration, animals were sacrificed for further analysis. The results demonstrated that stachydrine treatment effectively attenuated IND-induced acute gastric injury, as evidenced by reduced gastric myeloperoxidase activity, and pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1β). Stachydrine also significantly decreased gastric malondialdehyde activity while enhancing superoxide dismutase activity. Furthermore, it suppressed the expression of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and inducible nitric oxide synthase (iNOS) expressions. These findings indicate that stachydrine confers gastroprotection against IND-induced gastric injury, potentially by suppressing inflammatory and oxidative stress responses, inhibiting the ERK, AKT and iNOS signaling pathways. Thus, stachydrine may serve as a promising candidate for the treatment of IND-induced gastric injury.