Abstract: OBJECTIVE: To identify active compounds in an Yinyanghuo(Herba Epimedii Brevicornus)-Xianmao(Rhizoma Curculiginis) drug pair(ECD) and investigate its efficacy on polycystic ovary syndrome(PCOS), and its possible mechanism in a rat model of PCOS.METHODS: A network pharmacology approach involving a characteristic drug assessment, active compound and target prediction, PCOS gene collection as well as network analysis was employed.The ovary morphology after treatment was observed using an animal model and western blotting and real-time PCR were used to verify AKT1 as the molecular target.RESULTS: Six networks were constructed, an active compound-target network for the ECD(C-T network), a drug-target network(D-T network), a related genes network, a targets interaction network, a key genes interaction network, and a gene-pathway network. A total of 41 compounds and 261 targets were identified for the ECD, 232 PCOS-related genes, 31 cogenes, and 14 pathways. These pathways may be involved in the efficacy of ECD on PCOS. The proteins most involved in the signal pathways for all targets were AKT1,IL6, INSR, ESR, and GSK3B. The AKT1 target was selected for experimental verification. Based on the Western blot and real-time PCR results, the expression of AKT1 in the PCOS model varied after treatment with ECD.CONCLUSIONS: Our findings suggest that the ECD can reverse the negative morphological changes in ovarian tissue that occur in model rats of PCOS.AKT1 may be a key mediator of the observed ability of the ECD to protect against PCOS in the model rats.

Key words: polycystic ovary syndrome, Pharmacology, Yinyanghuo(Herba Epimedii Brevicornus) Xianmao(Rhizoma Curculiginis) drug pair