The therapeutic intervention of Chinese herbal formula SQQT on gastric mucosal spasmolytic polypeptide-expressing metaplasia cells and its systematic biological mechanism analysis
Objective:This study aimed to investigate the therapeutic impact of SQQT on the pathological phe-notype of spasmolytic polypeptide-expressing metaplasia(SPEM)cells in the gastric mucosa,and to explore the potential mechanisms underlying its intervention in the pathological evolution of SPEM cells.Methods:Retrospec-tive analysis was conducted to assess SQQT's effect on gastric precancerous lesions and SPEM cell distribution.In a murine model,the effect of SQQT on SPEM cytopathic phenotype was evaluated.A"component-target"net-work map was constructed using chromatography,single-cell RNA data,and network pharmacology analysis,fol-lowed by topological analysis.Results:①SQQT effectively alleviated gastric mucosal atrophy,intestinal metapla-sia,and dysplasia in patients with precancerous gastric lesions,and reduced SPEM cell formation at the gastric mucosal base;②Notably,SQQT significantly reduced the count of SPEM cells in the gastric mucosa of mice in-duced by the tamoxifen compound method,effectively targeting and suppressing the abnormal expression of key marker proteins such as Ki67 and CD44v9.③ This study identified a total of 27 components and 118 targets from the compound that are intimately associated with the pathological transition of proliferating SPEM cells.Topologi-cal analysis revealed that SQQT primarily regulates cellular processes including energy metabolism,ribosomal function,cell communication,and apoptotic signaling pathways,thereby exerting a profound impact on SPEM cell proliferation and differentiation.Intriguingly,six specific chemical constituents—Citric acid,Root bark phenol,Demethylated ruthenic amide,Wu Zhu Yu Huang alkaloid,Hesperidin,and Ginsenoside Re—were implicated in regulating critical biological functions such as mitochondrial ATP synthesis electron transport,redox membrane transporter activity,and ribosome function in SPEM cells,potentially constituting the material basis for com-pound regulation of SPEM cell pathology.Conclusion:The traditional Chinese medicine compound SQQT effec-tively suppresses abnormal proliferation and differentiation of SPEM cells in the gastric mucosa by harnessing the synergistic effects of multiple components targeting diverse biological pathways.