Work

Banxia Xiexin decoction alleviates N-methyl-N′-nitro-N-nitrosoguanidine-induced gastric precancerous lesions by modulating the gastric microbiota

Year: 2026

Type: article

Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD) is a traditional herbal formula with a history spanning over a millennium, significantly contributing to the treatment of gastrointestinal disorders, especially gastric precancerous lesions (GPL) such as gastritis, intestinal metaplasia, and dysplasia. Although it is effective in reducing inflammation, enhancing intestinal metaplasia, and providing antitumor benefits, the exact mechanisms of its action are not yet understood. AIM OF THE STUDY: This study aims to clarify how BXD influences the gastric microbiota to enhance GPL. MATERIALS AND METHODS: A GPL model was developed using N-Methyl-N'-nitro-N-nitrosoguanidine. The pharmacological effects of BXD on GPL were evaluated using ELISA, qPCR, AB-PAS staining, immunohistochemistry, H&E staining, Western blotting, and immunofluorescence. Subsequently, the protective effects of BXD against MNNG-induced GES-1 cells were evaluated in vitro. Furthermore, network pharmacology was employed to analyze the underlying mechanisms of BXD in the treatment of GPL. 16S rRNA sequencing was further employed to examine the structure and stability of the gastric microbiota. Finally, the roles of Lactobacillus and Streptococcus in GPL were further validated through animal experiments. RESULTS: The BXD intervention decreased TNF-α, IL-1β, and IL-6 levels in both gastric tissue and serum of GPL mice, enhanced IL-10 production, ameliorated intestinal metaplasia, and suppressed Ki67 and p53 expression. BXD mitigated gastric mucosal injury by upregulating the expression of Zonula occludens-1, E-cadherin, and Occludin, as well as inhibiting the PI3K-Akt and MAPK signaling pathways. Furthermore, BXD improved the dysbiosis of the gastric microbiota in GPL mice.The gastric microbiota of mice at the phylum level predominantly consisted of Bacillota, Proteobacteria, Cyanobacteria, Bacteroidota, Actinobacteria, Desulfobacterota, and Campylobacterota.In GPL mice, dysbiosis was notably marked by an increased presence of Bacillota and Proteobacteria, with Lactobacillus and Streptococcus at the genus level being significant contributors to GPL progression. The BXD intervention restored gastric microbiota balance by enhancing Bacillota and Lactobacillus abundance while reducing Proteobacteria and Streptococcus richness. Further intervention with Lactobacillus improved gastric mucosal atrophy and intestinal metaplasia associated with GPL, leading to a reduction in the levels of TNF-α, IL-1β, and IL-6 in gastric tissues, while enhancing the production of IL-10. This treatment also promoted the expression of Zonula occludens-1, E-cadherin, and Occludin, and inhibited the activation of the PI3K-Akt and MAPK signaling pathways. In contrast, treatment with Streptococcus in GPL mice resulted in more severe gastric mucosal atrophy and intestinal metaplasia, marked by increased levels of TNF-α, IL-1β, and IL-6, reduced IL-10 production, no significant increase in the expression of Zonula occludens-1, E-cadherin, and Occludin, and enhanced activation of the PI3K-Akt and MAPK signaling pathways. CONCLUSION: BXD intervention demonstrated significant therapeutic effects in GPL mice. The underlying mechanisms are associated with the restoration of gastric microbiota dysbiosis, promotion of beneficial bacterial growth, suppression of potential pathogens, modulation of the inflammatory response, and alleviation of mucosal damage.

Source: Journal of Ethnopharmacology

DOI: 10.1016/j.jep.2026.121409