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 a primary cause of gastric mucosal damage and inflammation, and its persistent presence is recognized as a major risk factor for the development of gastric cancer. Despite available treatments, eradication of H. pylori remains a significant clinical challenge, highlighting the urgent need for new therapeutic agents that can disrupt bacterial colonization and facilitate its elimination. Jiawei Lianpu Yin (JWLPY), a traditional herbal formula composed of natural medicinal substances, has been used to treat gastric disorders related to H. pylori infection. However, the precise mechanisms underlying its therapeutic effects have not yet been fully elucidated.

[AIM OF THE STUDY] The aim of this study was to investigate whether JWLPY can inhibit H. pylori colonization, alleviate gastric mucosal inflammation and damage, and to explore its underlying mechanisms of action.

[MATERIALS AND METHODS] The effects of JWLPY on H. pylori and gastric mucosal injury were evaluated both in vitro and in vivo, using a rat model of H. pylori induced gastritis and an in vitro model of H. pylori induced damage in human gastric mucosal epithelial cells. The mechanisms of action of JWLPY were further investigated through transcriptomic analysis, network pharmacology, and bioinformatics approaches.

[RESULTS] JWLPY inhibited the aggregation of inflammatory cells and preserved the integrity of the mucosal barrier, while reducing autophagy and apoptosis in gastric mucosal epithelial cells. Network pharmacology and transcriptomic analyses revealed that JWLPY promotes the assembly and synthesis of MUC5AC in the endoplasmic reticulum by activating the IRE1 XBP1 signaling pathway. This activation enhances protein folding and assembly processes within 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 tissue damage, and holds potential as a therapeutic agent for the treatment of H. pylori related gastritis.