Study on the Mechanisms and Experimental Verification of Cuscuta-Salvia (Tusizi-Danshen) in the Treatment of Polycystic Ovary Syndrome (PCOS) via Network Pharmacology

Abstract

\n Polycystic ovary syndrome (PCOS) is a sort of endocrine disease associated with Reproduction. The formula of Cuscuta-Salvia has been widely used in treatment of PCOS in clinic. However, its chemical and pharmacological are still not known in detail. First, the active components of Cuscuta-Salvia were identified by UHPLC-ESI-Q-TOF-MS and screened from TCMSP database, and the disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were obtained via a Venn diagram. Second, a protein-protein interaction (PPI) network was established. Core genes were selected using Cytoscape software plugin. Third, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for common targets using “pathview” package in R. Finally, several core targets were verified via determination of qRT-PCR and HE staining. Combined UHPLC-ESI-Q-TOF-MS analysis with network pharmacology study, 14 active components were obtained. Eighty common targets were also obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drug, response to oxygen levels, response lipopolysaccharide, and response to molecule of bacterial origin in biological process (BP) category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in cellular component (CC) category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in molecular function (MF) terms. KEGG enrichment pathway mainly involves in PI3K−Akt signaling pathway, MAPK signaling pathway, cellular senescence, TNF signaling pathway, and IL-17signaling pathway. Furthermore, based on an experimental study, Cuscuta-Salvia ameliorated the pathology of ovary, live and adipose tissue. Additional, Cuscuta-Salvia increased the mRNA expression of VEGFA. Cuscuta-Salvia decreased the mRNA expression of IL6, AKT1, TP53, MAPK1, JUN, EGF, AR, LHb, CYP17a1, and CYP19a1. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacology basis in an experimental model of PCOS via the regulation of the gene expression. This study lays a basis for subsequent research and clinical application.