Traditional herbal medicine Hyangsapyeongwi-san inhibits alcohol-induced gastric injury in mice by regulating NLRP3 inflammasome signaling

초록

Ethnopharmacological relevance: Hyangsapyeongwi-san (HPS), known as Xiangsha Pingwei San in Chinese medicine, is a classical herbal formula composed of ten medicinal herbs that has been traditionally used in traditional Korean medicine and East Asian medicine for centuries to treat gastrointestinal disorders associated with digestive impairment, including functional dyspepsia and gastritis. In traditional Korean medicine theory, these conditions correspond to "dampness-heat accumulation" and "qi stagnation" patterns affecting the spleen and stomach. HPS is formulated to "eliminate dampness, strengthen the spleen, and regulate qi circulation"-a traditional rationale for which the present study provides molecular evidence by demonstrating suppression of key inflammatory signaling pathways underlying gastric mucosal injury. Aim of study: This study aimed to investigate the gastroprotective effects of HPS against acute gastric injury and to elucidate its underlying molecular mechanisms, with a focus on NLRP3 inflammasome activation. Materials and methods: Male ICR mice were administered HPS (75 or 300 mg/kg) or ranitidine (40 mg/kg) orally once daily for 4 days prior to HCl/ethanol-induced gastric injury. Gastric damage, NLRP3 inflammasome components, inflammatory cytokines, signaling pathways, and apoptosis markers were assessed. Antiinflammatory effects were further evaluated in TNF-alpha-stimulated MKN45 gastric epithelial cells. Results: HPS dose-dependently reduced gastric damage scores and preserved mucosal architecture. High-dose HPS significantly suppressed IL-1(3 protein, IL-1(3 mRNA, and TNF-alpha mRNA expression. HPS inhibited NLRP3 inflammasome activation by reducing NLRP3 and caspase-1 levels, suppressed AKT and NF-kappa B p65 phosphorylation, and prevented apoptosis. In gastric epithelial cells, HPS attenuated IL-6 and IL-8 expression without cytotoxicity. Conclusion: HPS protects against acute gastric injury through NLRP3 inflammasome inhibition via the AKT/NF kappa B pathway, providing molecular evidence that supports its traditional use for digestive disorders.

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