Investigating the mechanism of Liang-Fu Dropping Pills in anti-gastric ulcer effects based on the PI3K-AKT signaling pathway

WANG Chang-fu; PAN Jie; LIAO Yong-e; LU Yuan; LIU Chun-hua; SUN Jia; ZHENG Lin; MA Xue; LI Yong-jun

doi:10.20251/j.cnki.1003-3734.2025.16.011

Abstract：Objective:To investigates the mechanism by which Liang-Fu Dropping Pills regulate the PI3K-AKT signaling pathway to exert an anti-gastric ulcer effect.Methods:First,the prepared Liang-Fu Dropping Pills,Alpinia officinarum,and Rhizoma Cyperi extracts were respectively detected and analyzed by ultra-high performance liquid chromatography-quadrupole-electrostatic orbitrap high-resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS).Subsequently,the potential pharmacological substances and potential mechanisms of action for the anti-gastric ulcer of Liang-Fu Dropping Pills were predicted through network pharmacology.Finally,in vivo experiments were conducted to investigate the anti-gastric ulcer effect of Liang-Fu Dropping Pills by observing the apparent morphology of the stomach and examining the stained tissues using histological staining methods.Real-time quantitative PCR and Western blotting were used to verify the regulatory effect of Liang-Fu Dropping Pills on potential targets in rat tissues of gastric ulcer model.Results:A total of 77 chemical constituents were identified from the extract of Liang-Fu Dropping Pills.Pathway enrichment analysis of chemical constituents and common targets of gastric ulcer disease showed that the anti-gastric ulcer mechanism of Liang-Fu Dropping Pills might be related to the regulation of lipid metabolism and PI3K-AKT signaling pathways.Molecular docking showed that protein kinase B1(AKT1)and cellular tumor antigen P53(TP53)were well combined with galangin and rhamnocitrin,the main index components of Liang-Fu Dropping Pills.In vivo experimental results showed that Liang-Fu Dropping Pills could significantly increase the level of acidic mucopolysaccharide(P<0.05)in the gastric mucosa,and significantly down-regulate the mRNA and protein expression levels of p-PI3K/PI3K(P<0.01),p-AKT/AKT(P<0.001),nuclear factor-kappa B p65[NF-κB p65(P<0.001)]and TP53(P<0.01)in the gastric ulcer tissue of rats.Conclusion:In this study,we preliminarily explored the mechanism of the anti-gastric ulcer effect of Liang-Fu Dropping Pills through network pharmacology and animal experiments,which may be related to the regulation of PI3K-AKT related signaling pathway,which provided a reference for in depth study of the pharmacodynamic material basis and mechanism of action Liang-Fu Dropping Pills.