Study on molecular mechanism Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma in the treatment of ulcerative colitis based on network pharmacology and molecular docking / 国际中医中药杂志

ABSTRACT

Objective:To investigate the pharmacological effects and molecular mechanisms of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma for the treatment of ulcerative colitis based on the network pharmacology and molecular docking methods.Methods:TCMSP database was applied to get the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma, and SwissTargetPrediction database was applied to predict their targets; OMIM, DrugBank, TTD, PharmGKB and GeneCards databases were used to obtain the disease targets of ulcerative colitis; Venn Diagram website was used to draw the venn diagrams of drug-disease intersecting targets; drug-component-target network diagrams were created in Cytoscape 3.8.2, and the targets and active components with high correlation in the network were analyzed; protein interaction networks of intersecting targets were constructed using the String platform, and the NetworkAnalyzer plug-in in Cytoscape 3.8.2 was applied to Topology analysis and screening of core targets were performed using the Metascape platform; GO and KEGG analysis were performed using the Metascape platform; molecular docking validation was performed using vina inside pyrx software.Results:A total of 14 active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma were screened, and the core components were kaempferol, stigmasterol, hederagenin, α-amyrin; 148 drug targets, 1 307 disease targets and 50 drug-disease intersection targets were obtained; there were 23 core points such as ESR1, PTPN2, PIK3R1, SRC, EGFR, and AKT1. The results of GO analysis indicated that the targets were mainly located in the cell membrane region and were involved in the regulation of biological functions such as monooxygenase and oxidoreductase activities, as well as the regulation of hormones and lipids, etc. The results of KEGG pathway enrichment analysis revealed that the main enrichment pathways were PI3K-Akt, JAK-STAT and MAPK signaling pathways. The molecular docking results showed that the main components, kaempferol and serpentine, could bind stably to several core targets such as PIK3R1 and ESR1. Relevant literature has verified the pharmacological action of each core component.Conclusions:Kaempferol, hederagenin and α-amyrin are the active components of Ginseng Radix et Rhizoma, Poria and Atractylodis Macrocephalae Rhizoma. They play therapeutic roles in improving immune dysregulation, reducing inflammatory response, inhibiting epithelial cell apoptosis and repairing mucosal damage by regulating targets such as PIK3R1, PTPN2 and ESR1, and modulating PI3K-Akt pathway, JAK-STAT pathway and MAPK pathway.