Huangjin Shuangshen decoction alleviates chronic atrophic gastritis by suppressing TNF/NF-κB signaling and promoting CFTR-associated gastric mucosal barrier repair
TL;DR
HJSS alleviates MNNG-induced CAG by attenuating inflammatory injury and promoting the recovery of gastric mucosal barrier-associated molecular features, supporting an inflammation–barrier mechanism underlying the action of HJSS in CAG.
Abstract
Background Chronic atrophic gastritis (CAG) is a precancerous gastric lesion characterized by persistent inflammatory injury, glandular atrophy, and impairment of gastric mucosal barrier-associated integrity. Huangjin Shuangshen Decoction (HJSS) has shown therapeutic potential in gastritis-related disorders, but its effects on CAG and the underlying mechanism remain unclear. This study investigated whether HJSS alleviates CAG by modulating inflammation-associated barrier dysfunction. Methods CAG was induced in mice by MNNG combined with ranitidine and irregular feeding, followed by treatment with different doses of HJSS, with folic acid as a positive control. Histopathology, gastric function indices, inflammatory mediators, apoptosis-related markers, and barrier-associated molecules were assessed in vivo. MNNG-injured GES-1 cells treated with HJSS-medicated serum were used for in vitro validation. Transcriptomic analysis, network pharmacology, and pharmacological inhibition were integrated to explore the underlying mechanisms. Results HJSS alleviated gastric mucosal atrophy and histopathological injury, improved gastric functional impairment, reduced inflammatory burden, and attenuated apoptosis-associated epithelial injury in experimental CAG. HJSS also promoted the recovery of gastric mucosal barrier-associated molecules, including CFTR, ZO-1, MUC5AC, Occludin, and Claudin-1. Integrated transcriptomic and network pharmacology analyses highlighted an inflammation–barrier framework involving TNF-related signaling and CFTR-associated regulation. In vitro, HJSS mitigated MNNG-induced epithelial injury, whereas CFTR inhibition attenuated the HJSS-associated restoration of CFTR and ZO-1. HJSS was further associated with suppression of TNF/NF-κB signaling and reduced p65 nuclear translocation. Conclusion HJSS alleviates MNNG-induced CAG by attenuating inflammatory injury and promoting the recovery of gastric mucosal barrier-associated molecular features. Its protective effects are associated with suppression of TNF/NF-κB signaling and involvement of CFTR-associated regulation, supporting an inflammation–barrier mechanism underlying the action of HJSS in CAG.