[Mechanism of Ziyin recipe for treatment of ovulatory infertility: a network pharmacology-based study and clinical observations].

Abstract

OBJECTIVE\nTo explore the mechanisms of Ziyin recipe for treatment of ovulatory infertility based on network pharmacology analysis and evaluate the clinical efficacy of this recipe.\n\n\nOBJECTIVE\nTCMSP, PubChem, Genecards, String, Swiss Target Prediction, and Uniprot databases were searched to identify all the action targets of Ziyin recipe and ovulatory infertility to construct the PPI network. Gene ontology (GO) and KEGG pathway enrichment analyses were performed and the TCM-active ingredient-target-pathway network was constructed using Cytoscape 3.6.0. We also designed a controlled clinical trial to verify the clinical effectiveness of Ziyin recipe. The patients were randomized into 2 groups to receive treatment with Western medicine including CC and HMG (control group) and additional treatment with Ziyin recipe, and the dosage of GN, follicular development days, E2 level of a single dominant follicle on trigger day, ovulation rate, the rate of LUFS, and clinical pregnancy rate were compared between the two groups.\n\n\nOBJECTIVE\nWe identified 22 active ingredients and 354 targets of action in Ziyin recipe, 791 targets of ovulatory infertility, and 96 common targets of action shared by Ziyin recipe and ovulatory infertility. According to Degree, the key targets included SRC, MAPK1, HSP90aa1, MAPK3, PTPN11, ESR1, Akt1, EGFR, NR3C1 and KNG1. Enrichment analysis of GO biological process showed that Ziyin recipe mainly focused on steroid hormonemediated signaling pathway, oxidation, reduction, and apoptosis. The most significantly enriched signaling pathways included PI3K-Akt signaling pathway, RAP1 signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, ovarian steroid production, and steroid hormone biosynthesis. The results of the clinical trial showed that Ziyin recipe significantly reduced the dose of GN, accelerated follicle development, increased E2 level of single dominant follicle on the trigger day, and increased the cycle ovulation rate and pregnancy rate.\n\n\nOBJECTIVE\nThe therapeutic effects of Ziyin recipe are probably mediated through different pathways to promote follicle development, thus improving ovulation rate and clinical pregnancy rate of infertile patients with ovulatory disorders.