Mechanism of Wenjing Decoction(温经汤)in Treating Polycystic Ovarian Syndrome Based on Network Pharmacology and Animal Experiments
Objective:To explore the mechanism of Wenjing Decoction(温经汤)in treating polycystic ovarian syndrome(PCOS)based on net-work pharmacology and animal experiments.Methods:The main active components and targets of Wenjing Decoction and the disease targets of PCOS were searched in TCMSP,BATMAN-TCM,Gene Cards,and Dis Genet databases,respectively,and the intersection of drug targets and disease targets was taken.Protein-protein interaction analysis was performed using the STRING database.Gene ontology(GO)function en-richment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed using the Metascape platform.The PCOS mice model was induced by letrozole combined with high-fat diet,and different doses of Wenjing Decoction were adminis-tered to observe the changes in body weight,fasting blood glucose level,and pathological morphology of ovarian tissue of rats.Enzyme-linked immunosorbent assay(ELISA)and immunohistochemistry were used to detect the expression of the core targets and core pathways in the blood and ovarian tissue of rats.Results:A total of 253 active ingredients were screened in Wenjing Decoction,mainly including Celabenzine,Glycyrol,paeoniflorgenone,evodiamine,etc.118 common targets were obtained after intersected with 536 disease targets,and core targets in-cluded protein kinase B α(AKT1),TP53,signal transducer and activator of transcription 3(STAT3),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA),interleukin-6(IL-6),epidermal growth factor receptor(EGFR),etc.GO enrichment in BP mainly in-cluded hormone response,peptide reaction,protein phosphorylation,etc.MF mainly included protein homodimer activity,heme-binding pro-tein,tetrapyrrole binding,etc.CC mainly includes nuclear membrane,lateral membrane,membrane raft,etc.KEGG enrichment discovered that signaling pathways such as hypoxia-inducible factor-1α(HIF-1α),phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),and TNF could play a key role in the treatment of PCOS by Wenjing Decoction.The results of animal experiments showed that compared with the normal control group,the body weight change was significantly increased in the model control group(P＜0.01),the fasting blood glucose level was increased significantly(P＜0.05),the serum levels of IL-6 and TNF-α were significantly increased(P＜0.01),the expression of VEGFA in ovarian tissue was significantly up-regulated,while the expressions of AKT and HIF-1α were significantly down-regulated(P＜0.01).The number of primordial follicles in ovarian tissue was increased,the number of cell layers of follicular granules was decreased,and the ovarian index was significantly reduced(P＜0.05).Compared with the model control group,the body weight change of rats was significantly reduced in Wenjing Decoction with doses of 10.14,20.28,and 40.56 g/kg(P＜0.05),the serum levels of IL-6 and TNF-α were significantly reduced(P＜0.01),the expression of VEGFA in ovarian tissue was significantly down-regulated,while the expressions of AKT and HIF-1α were sig-nificantly up-regulated(P＜0.01 or P＜0.05).The thickness of the cell layer of follicular granules was increased,the number of corpus lute-um was increased,and follicles at various developmental stages were observed.Conclusion:Wenjing Decoction can interfere with the expres-sion of PI3K/AKT/HIF-1α/VEGF signal pathway-related protein in ovarian tissue and reduce inflammatory reaction,which may be one of the mechanisms of Wenjing Decoction in the treatment of PCOS.
Wenjing Decoction(温经汤)Polycystic ovarian syndromeNetwork pharmacologyVascular endothelial growth factorProtein kinase B
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