Abstract:
OBJECTIVE To study the mechanism of Coptidis Rhizoma-Magnoliae Officinalis Cortex on inhibition of Helicobacter pylori(Hp) infection based on network pharmacology and experimental verification.
METHODS The main active components and target of Coptis Chinensis and Magnoliae Officinalis Cortex were screened out by TCMSP database, and the related targets of Hp infection were screened out by Drugbank, Genecards and DisGeNET database and Cytoscape 3.7.2 software was used to construct the drug-components-potential target network. The protein interaction network was constructed using String database to screen out the core targets. Metascape database was used to enrich GO and KEGG of intersection targets. Autodock Vina 1.1.2 was used to dock the main active ingredients and corresponding key targets of Coptidis Rhizoma-Magnoliae Officinalis Cortex drug pairs. Finally, the bacteriostatic effect of Coptidis Rhizoma-Magnoliae Officinalis Cortex was verified by in vitro bacteriostatic experiment, in animal experiments, ELISA and Western blotting were used to verify the related inflammatory factors and proteins in gastric mucosa of rats.
RESULTS There were 23 main active components of Coptidis Rhizoma and Magnoliae Officinalis Cortex, 185 targets, and 73 intersection targets with diseases. The core components were quercetin, berberine, magnolol and honokiol, and the core targets were TP53, IL-6, VEGFA, TNF and AKT1. The results of enrichment analysis showed that Coptidis Rhizoma-Magnoliae Officinalis Cortex drugs against Hp infection mainly involved TNF signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway and C-type lectin receptor signaling pathway. Molecular docking showed that quercetin, berberine, magnolol and honokiol had good binding activities with core targets TP53, IL-6, VEGFA, TNF and AKT1. The bacteriostatic zone of Coptidis Rhizoma-Magnoliae Officinalis Cortex pair was similar to that of clarithromycin, and the minimum bacteriostatic concentration was 31.3 mg·mL−1, which showed strong bacteriostatic effect in vitro; the results of animal experiments showed that compared with the model group, the contents of IL-1β, IL-6 and TNF-α in the serum of the Coptidis Rhizoma-Magnoliae Officinalis Cortex drug treatment groups were significantly decreased(P<0.05 or P<0.01), and the protein expressions of P53, AKT1 and TNF-α in the medicine pair group were decreased(P<0.05).
CONCLUSION This study confirms the multi-component, multi-target and multi-pathway mechanism of Coptidis Rhizoma-Magnoliae Officinalis Cortex drug pair against Hp infection, mainly by inhibiting bacterial growth, participating in inflammatory response, cell migration and proliferation, providing a basis for the study of the mechanism of Coptidis Rhizoma-Magnoliae Officinalis Cortex against Hp infection.