Berberine against Chronic Atrophic Gastritis by Inhibiting the SDF-1α and p-NF-κB Signaling Pathways

Abstract

Background: Chronic atrophic gastritis (CAG) is a prevalent gastrointestinal disorder characterized by gastric inflammation and epithelial cell impairment. Berberine, renowned for its potent anti-inflammatory, antioxidant, and immunomodulatory properties, is frequently utilized in managing gastrointestinal disorders and chronic inflammatory conditions. This study aimed to investigate the protective effects of berberine against CAG in mice and its underlying molecular mechanisms. Methods: CAG was induced in mice through Helicobacter pylori (Hp) infection and ethanol administration. Subsequently, mice were treated with varying doses of berberine (10 and 50 mg/kg). The therapeutic efficacy of berberine was evaluated by analyzing histopathological alterations, serum inflammatory markers, and oxidative stress levels. Moreover, the expression levels of stromal cell-derived factor-1 alpha (SDF-1α), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and proteins related to the nuclear factor-kappa B (NF-κB) signaling pathway were examined through Western blot analysis and immunohistochemistry. Results: Compared to the CAG group, berberine treatment can significantly improve CAG-related histopathological changes, reduce inflammatory infiltrating cells, and reduce gastric gland atrophy and epithelial cell damage. Berberine administration also reduced the levels of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and cyclooxygenase-2 (COX2) compared to the CAG group. Additionally, berberine downregulated the expression of SDF-1α, CXCR4, VEGF, and NF-κB p65 in gastric tissue, suggesting its inhibitory effect on these signaling pathways. Conclusion: This study demonstrates that berberine exerts protective effects against CAG in mice by suppressing the SDF-1α-CXCR4-VEGF and NF-κB signaling pathways. These findings underscore the potential utility of berberine in managing CAG and provide a basis for further investigation into its clinical applicability.