Polycystic ovary syndrome (PCOS) is a common reproductive metabolic disorder, normally accompanied by insulin resistance (IR). The specific pathogenesis of this disease remains unclear. To identify the underlying pathogenesis of PCOS with IR and explore the potential efficacy and mechanism of Jiawei Huanglian-Wendan decoction (JHWD) by a network pharmacology approach. The effective components and the potential drug and disease-related targets are retrieved. Drug-disease overlapped targets are being obtained by Venny analysis. The construction of protein-protein interaction network relied on Search Tool for the Retrieval of Interacting Genes/Proteins database (STRING), after uploading drug-disease overlapped targets. The drug-component-target-disease interaction network map was displayed , after importing their data into Cytoscape 3.7.2 software. Bioinformatics analyses are being performed by Metascape and Kyoto Encyclopedia of Genes and Genomes databases, respectively. Further, molecular docking analysis was carried out using AutoDock software. Finally, the influence of JHWD is verified by means of traditional Chinese medicine syndrome score, the rate of resumption of normal menstrual cycles and regular ovulation, the blood lipid levels, the blood glucose and insulin levels, and the inflammatory cytokines in PCOS with IR patients. Four primary interaction networks of JHWD are constructed. The enrichment analysis of PCOS-IR-related targets demonstrated that the top enriched pathways in the development of PCOS with IR are pathways in cancer, metabolic, phosphoinositide-3-kinase-protein kinase B signaling, lipid and atherosclerosis, and mitogen-activated protein kinase signaling pathways. Molecular docking analysis revealed strong binding interactions of the key targets with the active components. Further confirmations showed that the active components of JHWD exhibited significant clinical efficacy in improving the clinical syndromes, menstrual cyclicity and ovulatory function, and significantly reducing the blood lipid levels, blood glucose and insulin levels, and inflammatory cytokines in PCOS with IR patients. The combination of the network pharmacological analysis and clinical validation stated that the active compounds in JHWD could regulate glycolipid metabolism, reduce IR, and exert anti-inflammatory effects in the treatment of PCOS with IR, promoting Chinese classical formulations.
To investigate the mechanism of modified Huanglian Wendan decoction in the intervention of polycystic ovary syndrome (PCOS) by network pharmacology and molecular docking. The ingredients and targets of modified Huanglian Wendan decoction were retrieved from the traditional Chinese medicine Systems Pharmacology database. Related targets of PCOS were screened by Comparative Toxicogenomics Database database. Cytoscape 3.7.2 ( https://cytoscape.org/ ) was used to draw the target network diagram of “traditional Chinese medicine - ingredient - PCOS,” STRING database was used to construct the target protein interaction network. NCA tool of Cystoscape 3.7.2 was used to carried out topology analysis on PPI network, core components and key targets were obtained. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis were carried out for the intersection targets by David database. AutoDockTools 1.5.6 software ( https://autodock.scripps.edu/ ) was used to conduct molecular docking verification of key components and key targets. Ninety-one ingredients of the modified Huanglian Wendan decoction and 23,075 diseases targets were obtained, 155 Intersection targets of the drug and disease were obtained by R language, Veen plot was drawn. Gene ontology enrichment analysis obtained 432 biological processes, 67 cell components, 106 molecular functions. Fifty-four Kyoto encyclopedia of genes and genomes enrichment pathways ( P < .05) including tumor necrosis factor, hypoxia-induced factors-1, calcium, and drug metabolism-cytochrome P450 signaling pathway. Molecular docking showed quercetin, luteolin, kaempferol, and baicalein were stable in docking with core targets. Network pharmacology and molecular docking were used to preliminarily study the mechanism of action of modified Huanglian Wendan decoction in the treatment of PCOS, which laid foundation for future experimental research and clinical application.
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