Weimishu prescription alleviates liver-stomach disharmony and chronic gastritis by reducing inflammation and regulating gastric stem cell differentiation.

OBJECTIVE: To investigate the therapeutic effect of Weimishu prescription (, WMSP) on chronic gastritis with liver-stomach disharmony (CG-LSD) and elucidate its molecular mechanisms involved in regulating the nuclear factor kappa-B (NF-κB) inflammatory response and gastric stem cell (GSC) differentiation. METHODS: A CG-LSD rat model was established through a combined protocol involving 56% ethanol and tail-clip stimulation. Rats were administered with low-, medium-, or high-dose WMSP, the positive control drug omeprazole, or high-dose WMSP with the NF-κB agonist phorbol 12-myristate 13-acetate (PMA). Histopathological changes were assessed via hematoxylin and eosin and TdT-mediated dUTP nick end labeling staining. Flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were performed to evaluate the underlying mechanisms. RESULTS: WMSP significantly increased rat locomotor activity, improved Traditional Chinese Medicine syndrome scores, and ameliorated pathological damage to the gastric mucosa while reducing gastric mucosal epithelial cells apoptosis. WMSP also increased the proportion of Lgr5(+)Ki67(+) cells; upregulated muscle, intestine, and stomach specific transcript 1, sex determining region Y-box 2, sex determining region Y-box 9, and homing cell adhesion molecule; and enhanced the levels of pepsinogen C, somatostatin, mucin-6, H(+)-K(+)ATPase, and E-cadherin proteins, thereby promoting gastric stem cell survival and differentiation. Furthermore, WMSP alleviated systemic and gastric mucosal inflammation in CG-LSD rats. Mechanistically, WMSP suppressed NF-κB expression, thereby reducing Smad-specific E3 ubiquitin ligase 2 levels, which enhanced β-catenin and subsequently increased myelocytomatosis oncogene, and axis inhibition protein 2 expression. PMA administration reversed the protective effect of WMSP on CG-LSD rats. CONCLUSIONS: WMSP ameliorated gastric mucosal injury in CG-LSD rats by regulating the NF-κB/β-catenin signaling pathway, thereby suppressing inflammation and promoting gastric stem cell differentiation. These findings highlight the therapeutic potential of WMSP, providing the foundation for further clinical evaluations of WMSP in CG-LSD treatment.