Investigation of the mechanisms and experimental verification of Cuscuta-Salvia in the treatment of polycystic ovary syndrome (PCOS) via network pharmacology.

Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproduction. The Cuscuta-Salvia formula has been widely used to treat for PCOS in clinic. However, its chemical and pharmacological properties remain unclear. We identified the active components and related targets of Cuscuta-Salvia using UHPLC-ESI-Q-TOF-MS and TCMSP database. Disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were identified using a Venn diagram. PPI network was established. Core genes were selected using a Cytoscape software plugin. GO and KEGG enrichment analyses were performed for common targets using the "pathview" package in R. Several core targets were verified using molecular and Immunological methods. By combining UHPLC-ESI-Q-TOF-MS with a network pharmacology study, 14 active components and a total of 80 common targets were 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 drugs, response to oxygen levels, response lipopolysaccharides, and response to molecule of bacterial origin in BP category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in 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 MF terms. The KEGG enrichment pathway was mainly involved in the PI3K - Akt, MAPK, TNF, IL-17 signalling pathways, and in cellular senescence. Furthermore, the results of the experimental study showed that Cuscuta-Salvia ameliorated the pathological changes in the ovaries, liver and adipose tissue. And it improved the expressions of the genes or proteins. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacological basis in an experimental model of PCOS by regulating gene expression. This study provides a basis for future research and clinical applications.