Mechanism of Yishen Quzhuo Formula in Treating PCOS-IR Based on Network Pharmacology and Animal Experiments
LI Meng-yuan
GAO Zheng
XU Xin
Abstract：Objective:To investigate the mechanism of Yishen Quzhuo Formula in treating polycystic ovary syndrome with insulin resistance(PCOS-IR)through the network pharmacology and experimental validation.Methods:Active components and targets of Yishen Quzhuo Formula were retrieved from databases such as Traditional Chinese Medicine Systems Pharmacology(TCMSP).The targets of PCOS-IR-related disease were screened using GeneCards,OMIM,and DrugBank databases.A drug-component-target network was then constructed.Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)function,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using STRING and DAVID.Molecular docking was conducted with AutodockTools 1.5.7 software.A PCOS-IR rat model was established using the high-fat diet combined with letrozole.Serum hormone levels and glucose metabolism indices were evaluated.The expression of key targets was validated via Western blotting and quantitative polymerase chain reaction(qPCR).Results:A total of 136 potential active components of Yishen Quzhuo Formula and 406 PCOS-IR-related targets were identified.Five core components,including kaempferol,quercetin,and β-sitosterol,were selected.The top 10 key targets,such as interleukin-6(IL-6),signal transducer and activator of transcription 3(STAT3),protein kinase B1(AKT1),heat shock protein 90(HSP90),and tumor protein 53(TP53),were ranked by the degree values in the core network,enriched in the pathways like advanced glycation end product-receptor for advanced glycation end product(AGE-RAGE)and phosphoinositide 3-kinase(PI3K)-AKT.Animal experiments showed that Yishen Quzhuo Formula significantly reduced the levels of serum luteinizing hormone(LH),testosterone,fasting insulin(FINS),and homeostasis model assessment of insulin resistance(HOMA-IR)in PCOS-IR rats(all P＜0.05),and downregulated the expressions of STAT3,epidermal growth factor receptor(EGFR)and HSP90 in the ovarian tissues of PCOS-IR rats,while upregulated the expressions of AKT1 and TP53(all P＜0.05).Conclusions:Yishen Quzhuo Formula ameliorates the endocrine abnormalities and glucose metabolism disorders of PCOS-IR through multi-component,multi-target and multi-pathway mechanisms.
Keywords：Polycystic ovary syndromeInsulin resistancePharmacologyMolecular docking simulationYishen Quzhuo formulaNetwork pharmacology
Publication Date：2025-09-15
Online Publishing Date：2025-10-30(First online date of this platform, not the publication date of the document)
Pages：8( 353-360 )