To explore the mechanism of Kuntai Capsules in treating premature ovarian failure and menopausal syndrome based on the theory of simultaneous treatment of different diseases by network pharmacology and animal experiments.Methods:The active components and targets of Kuntai Capsules were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP) and a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM),and the disease targets were obtained from GeneCards,Online Mendelian Inheritance in Man(OMIM) and other databases.The common targets shared by Kuntai Capsules,premature ovarian failure,and menopausal syndrome were identified.The “drug-disease-common target” network and the protein-protein interaction(PPI) network were built.DAVID was used for gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.Furthermore,the rat model of premature ovarian failure and menopausal syndrome was established,and the modeled rats were randomized into blank control(sham operation),model,progynova(model+progynova),and Kuntai Capsules(model+Kuntai Capsules) groups(n=8).Enzyme-linked immunosorbent assay was employed to measure the levels of sex hormones including follicle-stimulating hormone(FSH),estradiol(E2) and luteinizing hormone(LH) in each group.The serum levels of interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α) were compared among different groups.Results:1) A total of 128 targets of Kuntai Capsules in the treatment of premature ovarian failure and menopausal syndrome were obtained,including glyceraldehyde-3-phosphate dehydrogenase(GAPDH),proto-oncogene tyrosine-protein kinase SRC,IL-6,TNF,and estrogen receptor 1(ESR1).The core targets were mainly enriched in cancer,hypoxia-inducible factor-1(HIF-1),phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT),and TNF signaling pathways.2) The results of animal experiments showed that the model group had higher FSH and LH levels and lower E2 level than the sham operation group.The Kuntai Capsules group had lower FSH and LH levels and higher E2 level than the sham operation group.Compared with the sham operation group,the model group showed elevated IL-6 and TNF-α levels(P<0.05).After intervention with Kuntai Capsules,the IL-6 and TNF-α levels declined(P<0.05).Conclusion:Kuntai Capsules may treat premature ovarian failure and menopausal syndrome by regulating the HIF-1,PI3K,and TNF signaling pathways via the core targets such as GAPDH,SRC,IL-6,and TNF.