Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Coptis chinensis Franchin Polycystic Ovary Syndrome

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.

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Investigation of the Mechanism of Zishen Yutai Pills on Polycystic Ovary Syndrome: A Network Pharmacology and Molecular Docking Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6843828 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Yingyin Chen ◽

Xinyi Chai ◽

Ying Zhao ◽

Xinqian Yang ◽

Caiting Zhong ◽

...

Keyword(s):

Molecular Docking ◽

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Polycystic Ovary Syndrome ◽

Target Genes ◽

Polycystic Ovary ◽

Network Pharmacology ◽

Analysis Tool ◽

Ovary Syndrome

Background. Zishen Yutai Pills (ZSYTP) is a prescription based on traditional Chinese medicine used to treat kidney-deficient pattern in traditional Chinese medicine. It is also widely used clinically for the treatment of polycystic ovary syndrome (PCOS) with positive results. This study aims to explore the potential pharmacological mechanism of ZSYTP for the treatment of PCOS by a network pharmacology approach. Methods. Compounds were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine and TCM Database@ Taiwan, and the corresponding targets were retrieved from PubChem, Swiss Target Prediction, STITCH, and DrugBank. Meanwhile, PCOS targets were retrieved from the GeneCards database, the Online Mendelian Inheritance in Man database, National Center for Biotechnology Information Database, and DrugBank. Subsequently, multiple network construction and gene enrichment analyses were conducted with Cytoscape 3.8.2 software. Based on the previous results in the study, molecular docking simulations were done. Results. 205 active compounds and 478 ZSYTP target genes were obtained after screening by ADME consideration. 1881 disease-related targets were obtained after removing duplicates. 148 intersection target genes between drug and disease targets were isolated. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis highlighted multiple gene functions and different signaling pathways to treat PCOS. Further molecular docking demonstrated the practicality of in vivo action of ZSYTP to a certain extent. Conclusions. It is possible that the pharmacological effect of ZSYTP on PCOS is linked to the hypoxia-inducible factor 1 (HIF-1) signaling pathway, improving insulin resistance, the variation on gene expression such as RNA splicing, and regulation of mRNA metabolic process. This study paves the way for further research investigating its mechanisms.

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Network Pharmacology-based Strategy for Predicting Active Ingredients and Potential Targets of Coptis Chinensis Franch in Polycystic Ovary Syndrome

10.21203/rs.3.rs-77454/v1 ◽

2020 ◽

Author(s):

Jianxiong Ma ◽

Miaoyong Ye ◽

Ke Ma ◽

Kang Zhou ◽

YingYing Zhang ◽

...

Keyword(s):

Gene Ontology ◽

Chinese Medicine ◽

Polycystic Ovary ◽

Interaction Network ◽

Network Pharmacology ◽

Active Ingredients ◽

Coptis Chinensis ◽

Ovary Syndrome ◽

R Language ◽

Bioactive Ingredients

Abstract Background: Polycystic ovary syndrome (PCOS) is a disease that causes low fertility in females. Coptis chinensis (CC) has been used to clear away heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although CC has demonstrated efficacy against PCOS in clinical practice, there is no available data regarding the bioactive ingredients, component targets, and confirmed molecular mechanism of this drug combination.Methods: A network pharmacology approach was applied to analyze the bioactive ingredients, component targets, and core signaling pathways of CC. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen effective active ingredients and targets of CC. The GeneCards, OMIM, and PharmGkb databases was utilized to screen disease targets for PCOS. R language software was used to screen common targets of drugs and diseases. Cytoscape software (version 3.7.1) 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. OmicShare tools was used to analysis Gene ontology (GO) biological function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) path enrichment. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes.Results: 14 effective active ingredients and 218 targets of CC were screened by TCMSP platform. 3517 disease targets for PCOS were obtianed by the disease database and 102 common targets of drugs and diseases were screened through R language software. Key targets of CC for the treatment of PCOS included JUN, MAPK, IL-6, CXCL8, FOS, and IL1B. A total of 123 Gene Ontology (GO) terms and 129 pathways were acquired by analyzing the enrichment of GO and KEGG. It is speculated that the AGEs/RAGE, TNF, IL-17, MAPK and HIF-1 signaling pathways are closely related to PCOS and may be the core pathways involved in PCOS. The molecular docking results showed that quercetin has a higher degree of binding to core targets (eg: IL-6, IL- 1β, MAPK, CXCL8) related to the inflammatory pathway.Conclusions: This preliminary study verified the basic pharmacological effects and mechanisms of CC, a Chinese medicine, in the treatment of PCOS. Particularly, the effect of CC on inflammation and glucose metabolism pathway was noteworthy. This study provides new insights for the systematic exploration of the mechanism of action of Chinese medicine.

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The Effects of Traditional Chinese Medicine-Associated Complementary and Alternative Medicine on Women with Polycystic Ovary Syndrome

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6619597 ◽

2021 ◽

Vol 2021 ◽

pp. 1-26

Author(s):

Wenjuan Shen ◽

Bao Jin ◽

Yujia Pan ◽

Yanhua Han ◽

Tianjiao You ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Symptom Relief ◽

Public Health Problem ◽

Signs And Symptoms ◽

Ovary Syndrome ◽

The Impact ◽

Complementary And Alternative

Polycystic ovary syndrome (PCOS) is a touchy clinical and public health problem worldwide, which adversely affects women’s health and health-related comorbidities for lifetime, and represents a tremendous burden for both the family of the patient and for society. According to the diagnostic criteria used and the population studied, the prevalence rate of PCOS is between 6% and 21%. However, current conventional modern medicines for PCOS are only moderately effective at controlling the signs and symptoms, while they are not thoroughly able to prevent complications. Therefore, many patients have turned to complementary and alternative medical (CAM) treatments. CAM use is wide spread among patients with PCOS, and more than 70% of patients use CAM at one point during their diseases. The patients’ primary motivations include dissatisfaction with available medications, perceive higher risk of drug side effects and crushing health burden and economic costs, desire for symptom relief, pursuit of shortening the course of disease, and the belief that CAM therapy is in accordance with the patients’ values and beliefs. At present, several CAM methods have been used in women with PCOS, which has achieved obvious effects. However, biologically plausible mechanisms of the action of traditional Chinese medicine- (TCM-) associated CAM for PCOS have not been systematically reviewed. This review briefly summarizes the current progress of the impact of herbal medicine on the outcomes of PCOS and introduces the mechanisms.

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Serum metabolomics study of Traditional Chinese medicine formula intervention to polycystic ovary syndrome

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2015.12.020 ◽

2016 ◽

Vol 120 ◽

pp. 127-133 ◽

Cited By ~ 12

Author(s):

Caixia Lu ◽

Xinjie Zhao ◽

Yan Li ◽

Yanjie Li ◽

Chengkun Yuan ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Chinese Medicine Formula ◽

Metabolomics Study ◽

Serum Metabolomics

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Network Pharmacology-Based Prediction of Bioactive Compounds and Potential Targets of Wenjing Decoction for Treatment of Endometriosis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/4521843 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yu-nan Liu ◽

Xiao-jing Hu ◽

Bei Liu ◽

Yu-jie Shang ◽

Wen-ting Xu ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Signaling Pathways ◽

Signaling Pathway ◽

Bioactive Compounds ◽

Interaction Network ◽

Enrichment Analysis ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Inflammatory Disorder

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the “TNF signaling pathway” and the “estrogen signaling pathway.” Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

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Investigation on the Use of Traditional Chinese Medicine for Polycystic Ovary Syndrome in a Nationwide Prescription Database in Taiwan

Journal of Clinical Medicine ◽

10.3390/jcm7070179 ◽

2018 ◽

Vol 7 (7) ◽

pp. 179 ◽

Cited By ~ 6

Author(s):

Wan-Ting Liao ◽

Jen-Huai Chiang ◽

Chia-Jung Li ◽

Ming-Tsung Lee ◽

Cheng-Chiung Su ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Polycystic Ovary Syndrome ◽

Large Scale ◽

Polycystic Ovary ◽

Reproductive Age ◽

Chinese Society ◽

Prescription Database ◽

Ovary Syndrome ◽

Beneficial Effects

Polycystic ovary syndrome (PCOS) is a common condition, affecting 5–10% of women of reproductive age worldwide. It has serious reproductive implications and causes mood disorders and metabolic disorders, such as type-2 diabetes. Because PCOS reflects multiple abnormalities, there is no single drug that can treat all its symptoms. Existing pharmaceutical agents, such as oral contraceptives (OCs), are suggested as a first-line therapy for menstrual irregularities; however, OCs are not appropriate for women pursuing pregnancy. Additionally, insulin-sensitizing agents, which appear to decrease insulin levels and hyperandrogenemia in women with PCOS, have been associated with a high incidence of gastrointestinal adverse effects. It is a common practice in Chinese society to receive traditional Chinese medicine (TCM) for treatment of gynecological problems and infertility. Current research demonstrates that several herbs and herbal formulas show beneficial effects in PCOS treatment. In this study, we conducted the first large-scale survey through the Taiwan National Health Insurance Program database to analyze TCM utilization patterns among women with PCOS in Taiwan during 1997–2010. The survey results revealed that 89.22% women with newly diagnosed PCOS had received TCM therapy. Jia-Wei-Xiao-Yao-San and Xiang-Fu (Rhizoma Cyperi) were the most commonly used formula and single herb, respectively, in the database. In addition, we found that the top five commonly prescribed single herbs and herbal formulas have shown promise in treating symptoms associated with PCOS.

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