Potential mechanisms by which Jiawei Lianpu Yin inhibits Helicobacter pylori colonization and alleviates gastric mucosal inflammation and damage: Integrated transcriptomics, network pharmacology, and experimental validation

Ethnopharmacological relevance: Helicobacter pylori (H.pylori) infection is the leading cause of gastric mucosal damage and inflammation, and persistent infection is one of the major risk factors for gastric cancer. Eradication of H.pylori remains a clinical challenge, and therefore, it is urgently necessary to identify more drugs that can interfere with H.pylori colonization and promote its clearance. Jiawei Lianpu Yin (JWLPY) is a compound formula composed of natural drugs used to treat gastric diseases associated with H.pylori infection. However, the underlying mechanisms of its action are still unclear. Aim of the study: The aim of this study was to investigate whether JWLPY can inhibits H.pylori colonization and alleviates gastric mucosal inflammation and damage and to explore its mechanism of action. Materials and METHODS: The effects of JWLPY on Helicobacter pylori and gastric mucosa injury were studied by using Helicobacter pylori induced gastritis model in rats. Transcriptomics, network pharmacology and bioinformatics were used to determine the mechanism of JWLPY Results: JWLPY inhibited the aggregation of inflammatory cells and preserved the integrity of the mucosal barrier, reducing autophagy and apoptosis in gastric mucosal epithelial cells. Network pharmacology and transcriptomics analysis revealed that JWLPY promotes the assembly and synthesis of MUC5AC in the endoplasmic reticulum by activating the IRE1-XBP1 signaling pathway, which enhances the process of protein assembly in the endoplasmic reticulum, thereby inhibiting H.pylori colonization in the gastric mucosa. Conclusion: This study is the first to demonstrate that JWLPY inhibits H.pylori colonization in the gastric mucosa, alleviates gastric inflammation and damage, and is a potential drug for the treatment of H.pylori -related gastritis. The effect of JWLPY on Helicobacter pylori and gastric mucosa injury in vivo was studied by using Helicobacter pylori induced gastritis model in rats. Transcriptomics, network pharmacology and bioinformatics were used to determine the mechanism of JWLPY Control* samples refer to the group that did not receive any intervention during the experiment. Model-* samples refer to the group in which gastritis was induced in rats using Helicobacter pylori infection. LPY-* samples refer to the group that received intragastric administration of Jiawei Lianpu Yin treatment based on the gastritis model.