Mechanism of Shaofu Zhuyu Decoction in treatment of EMT induced dysmenorrhea based on network pharmacology and molecular docking / 中国中药杂志

ABSTRACT

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) were searched for the effective components and targets of Shaofu Zhuyu Decoction. The relevant targets for endometriosis(EMT) and dysmenorrhea were retrieved from the Comparative Toxicogenomics Database(CTD), Therapeutic Target Database(TTD), GeneCards, and DisGeNET with the terms of "endometriosis" and "dysmenorrhea". Cytoscape 3.8.0 was employed to construct the drug-active component-therapeutic target network. A protein-protein interaction(PPI) network was established by STRING 11.0. Analyze Network, the plug-in in the Cytoscape 3.8.0, was used to calculate the topological parameters of the nodes and screen out the critical proteins in the network. The potential therapeutic targets were imported into RStudio and subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses with clusterProfiler package. Finally, the AutoDock Vina(Vina) platform was used for molecular docking to predict the binding degree of the main active components of Shaofu Zhuyu Decoction to key targets. As revealed by the screening results, 136 active components and 380 targets of Shaofu Zhuyu Decoction were obtained. Additionally, there were 1 627 targets related to EMT and 142 targets related to dysmenorrhea with 107 common targets, and 42 potential therapeutic targets of Shaofu Zhuyu Decoction for the treatment of EMT-induced dysmenorrhea. The targets such as interleukin 6(IL6) and prostaglandi-nendoperoxide synthase-2(PTGS2) were pivotal in the biological network of Shaofu Zhuyu Decoction intervention in EMT-induced dysmenorrhea, which involved multiple signaling pathways, including inflammation, hormones, and those promoted cell proliferation [e.g., mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3 kinase(PI3 K)-protein kinase B(AKT)]. The results of molecular docking showed that the active components of Shaofu Zhuyu Decoction had good binding capacities to key targets such as IL6 and PTGS2. The findings of this study demonstrated that Shaofu Zhuyu Decoction could treat EMT-induced dysmenorrhea through multiple targets and multiple pathways, which could provide new ideas for investigating the underlying mechanism of Shaofu Zhuyu Decoction in the treatment of EMT-induced dysmenorrhea.