Abstract
Background Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. Methods and Results Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1β). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. Conclusions This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine.
Highlights
Polycystic ovarian syndrome (PCOS) is an endocrine syndrome characterized by persistent anovulation, hyperandrogenemia, or insulin resistance and is the most common cause of infertility in women of childbearing age [1]
Among them, hydrogenated berberine acted on 31 targets, berberine acted on 16 targets, berberine acted on 13 targets, and quercetin acted on 139 targets, which are the more effective targets. e Uniprot database was used to collect the gene names of the active targets and delete invalid and duplicate targets, leading to a total of 148 active targets of C. chinensis
Collection of Polycystic Ovary Syndrome-Related Genes. e Genecards, OMIM, and PharmGkb disease databases were searched, and a total of 3,517 disease targets related to PCOS were collected. e R language was used to map the active targets of the active ingredients of C. chinensis to these disease targets
Summary
Polycystic ovarian syndrome (PCOS) is an endocrine syndrome characterized by persistent anovulation, hyperandrogenemia, or insulin resistance and is the most common cause of infertility in women of childbearing age [1]. Pharmacological studies have confirmed that C. chinensis has anti-inflammatory, antiallergenic, hypoglycemic, lipidlowering, and antioxidant properties [5, 6]. Of note, it can improve insulin resistance and impaired glucose tolerance in PCOS patients [7, 8]. Erefore, it is important to systematically and comprehensively study the material basis and mechanisms of action of C. chinensis to improve and treat PCOS. Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. E TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. Based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis
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