Wen-Wei-San-Ji Formula Ameliorates Chronic Atrophic Gastritis by Suppressing Epithelial-mesenchymal Transition

Abstract Objective: This study aimed to verify the therapeutic efficacy of the Wen-Wei-San-Ji (WWSJ) formula in treating chronic atrophic gastritis (CAG) and elucidate its underlying mechanism of action. Materials and Methods: A rat model of CAG and cellular models were used for in vivo and in vitro experiments, respectively. For in vivo animal experiments, the evaluation indicators included gastric mucosal morphology, gastric pH levels, gastric weight, and pathological changes. In vitro assays included cell counting kit-8, crystal violet staining, and wound healing assays. Liquid chromatography-tandem mass spectrometry was employed to analyze the chemical constituents of the WWSJ formula and the components of WWSJ-containing serum. Network pharmacology analysis was performed to predict the potential mechanism of WWSJ, which was further verified by immunohistochemical (IHC) staining, Western blotting, and quantitative real-time polymerase chain reaction. Results: WWSJ exerted a significant therapeutic effect on CAG in rats, effectively improving the pathological status of gastric mucosa without obvious toxicity. A total of 33 serum-entering components of WWSJ were identified. WWSJ-containing serum significantly inhibited the proliferation and migration of pathologically altered gastric mucosal epithelial cells, while exerting no significant effect on normal gastric mucosal epithelial cells. Network pharmacology analysis revealed that WWSJ could regulate multiple signaling pathways associated with epithelial-mesenchymal transition (EMT), a key process in the progression of CAG. Further in vivo and in vitro experiments confirmed that WWSJ could modulate the expression of EMT-related markers. Conclusions: The findings collectively demonstrate that WWSJ exerts its therapeutic effects on CAG by inhibiting the EMT process, thereby providing experimental evidence for the clinical application of the WWSJ formula.