A network pharmacology approach to explore active compounds and pharmacological mechanisms of epimedium for treatment of premature ovarian insufficiency

Background and purpose Premature ovarian insufficiency (POI) refers to a hypergonadotropic hypoestrogenism and the condition of pre-onset ovarian function failure. Epimedium is a common traditional Chinese herbal medicine that is widely used to relieve POI in China. To systematically explore the pharmacological mechanism of epimedium on POI therapy, a network pharmacology approach was conducted at the molecular level. Methods In this study, we adopt the network pharmacology method, which mainly includes active ingredients prescreening, target prediction, gene enrichment analysis and network analysis. Results The network analysis revealed that 6 targets (ESR1, AR, ESR2, KDR, CYP19A1 and ESRRG) might be the therapeutic targets of epimedium on POI. In addition, gene-enrichment analysis suggested that epimedium appeared to play a role in POI by modulating 6 molecular functions, 5 cellular components, 15 biological processes and striking 52 potential targets involved in 13 signaling pathways. Conclusion This study predicted the pharmacological and molecular mechanism of epimedium against POI from a holistic perspective, as well as provided a powerful tool for exploring pharmacological mechanisms and rational clinical application of traditional Chinese medicine.

[1]  Ronggen Wang,et al.  Effect of Hyperin and Icariin on steroid hormone secretion in rat ovarian granulosa cells. , 2019, Clinica chimica acta; international journal of clinical chemistry.

[2]  R. Dalgleish,et al.  Microsatellite variation of ESR1, ESR2, and AR in Serbian women with primary ovarian insufficiency , 2018, Climacteric : the journal of the International Menopause Society.

[3]  C. Sergiampietri,et al.  Estrogen treatment in infertile women with premature ovarian insufficiency in transitional phase: a retrospective analysis , 2018, Journal of Assisted Reproduction and Genetics.

[4]  K. Mehmood,et al.  Icariin Ameliorate Thiram-Induced Tibial Dyschondroplasia via Regulation of WNT4 and VEGF Expression in Broiler Chickens , 2018, Front. Pharmacol..

[5]  Yugui Cui,et al.  Curcumin exerts a protective effect against premature ovarian failure in mice , 2018, Journal of molecular endocrinology.

[6]  F. Zhang,et al.  Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro , 2018, Front. Mol. Neurosci..

[7]  M. Park,et al.  Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility , 2017, The world journal of men's health.

[8]  M. Tsai,et al.  A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer , 2017, Front. Pharmacol..

[9]  Chenxia Sheng,et al.  Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ1–42-Induced Rat Model of Alzheimer's Disease , 2017, BioMed research international.

[10]  Hyung‐Min Kim,et al.  Kaempferol impedes IL-32-induced monocyte-macrophage differentiation. , 2017, Chemico-biological interactions.

[11]  T. He,et al.  Epimedin C Promotes Vascularization during BMP2-Induced Osteogenesis and Tumor-Associated Angiogenesis. , 2017, The American journal of Chinese medicine.

[12]  Boxian Huang,et al.  Different therapeutic effects of cells derived from human amniotic membrane on premature ovarian aging depend on distinct cellular biological characteristics , 2017, Stem Cell Research & Therapy.

[13]  Jian Huang,et al.  Estrogen receptor-α36 is involved in icaritin induced growth inhibition of triple-negative breast cancer cells , 2017, The Journal of Steroid Biochemistry and Molecular Biology.

[14]  Xia Wang,et al.  PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database , 2017, Nucleic Acids Res..

[15]  Damian Szklarczyk,et al.  The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible , 2016, Nucleic Acids Res..

[16]  Ayesha,et al.  Premature Ovarian Failure: An Association with Autoimmune Diseases. , 2016, Journal of clinical and diagnostic research : JCDR.

[17]  R. Z. Liang,et al.  Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health. , 2016, Pharmacology & therapeutics.

[18]  X. Qin,et al.  Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology , 2016, Scientific Reports.

[19]  W. Xiao,et al.  Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach. , 2016, Journal of ethnopharmacology.

[20]  Zhongxing Peng,et al.  Icariin has synergistic effects with methylprednisolone to ameliorate EAE via modulating HPA function, promoting anti-inflammatory and anti-apoptotic effects. , 2015, International journal of clinical and experimental medicine.

[21]  Gang Fu,et al.  PubChem Substance and Compound databases , 2015, Nucleic Acids Res..

[22]  Jin-jian Lu,et al.  Chemical Constituents, Quality Control, and Bioactivity of Epimedii Folium (Yinyanghuo). , 2015, The American journal of Chinese medicine.

[23]  E. Kovanci,et al.  Premature ovarian failure: clinical presentation and treatment. , 2015, Obstetrics and gynecology clinics of North America.

[24]  Tatiana A. Tatusova,et al.  Gene: a gene-centered information resource at NCBI , 2014, Nucleic Acids Res..

[25]  P. Bruzzi,et al.  Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials. , 2014, Cancer treatment reviews.

[26]  D. Nègre,et al.  The RNA-binding protein Mex3b regulates the spatial organization of the Rap1 pathway , 2014, Development.

[27]  Yanqiong Zhang,et al.  A systems biology-based investigation into the therapeutic effects of Gansui Banxia Tang on reversing the imbalanced network of hepatocellular carcinoma , 2014, Scientific Reports.

[28]  A. Oto,et al.  The cardiovascular effects of premature ovarian failure. , 2013, International journal of cardiology.

[29]  Jiayin Liu,et al.  Estrogen receptor α gene (ESR1) polymorphisms associated with idiopathic premature ovarian failure in Chinese women , 2013, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[30]  Li'na Hu,et al.  Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. , 2011, The Cochrane database of systematic reviews.

[31]  N. Kim,et al.  Vascular endothelial growth factor gene polymorphisms in Korean patients with premature ovarian failure. , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[32]  Guan-hua Du,et al.  [Network pharmacology: new guidelines for drug discovery]. , 2010, Yao xue xue bao = Acta pharmaceutica Sinica.

[33]  A. Shelling.  Premature ovarian failure. , 2010, Reproduction.

[34]  A. Hopkins.  Network pharmacology: the next paradigm in drug discovery. , 2008, Nature chemical biology.

[35]  Alan F. Scott,et al.  McKusick's Online Mendelian Inheritance in Man (OMIM®) , 2008, Nucleic Acids Res..

[36]  C. Welt,et al.  Primary ovarian insufficiency: a more accurate term for premature ovarian failure , 2008, Clinical endocrinology.

[37]  L. Schover.  Premature ovarian failure and its consequences: vasomotor symptoms, sexuality, and fertility. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  R. Baber,et al.  Premature ovarian failure: a review , 2007, Climacteric : the journal of the International Menopause Society.

[39]  P. Chambon,et al.  Premature ovarian failure in androgen receptor-deficient mice. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  P. Touraine,et al.  Ovarian steroidogenesis and serum androgen levels in patients with premature ovarian failure. , 2005, The Journal of clinical endocrinology and metabolism.

[41]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[42]  Hung-Rong Yen,et al.  Pregnancy in premature ovarian failure after therapy using Chinese herbal medicine. , 2003, Chang Gung medical journal.

[43]  R. Dalgleish,et al.  Microsatellite variation of ESR 1 , ESR 2 , and AR in Serbian women with primary ovarian insufficiency , 2018 .

[44]  J. Frampton.  Triptorelin: A Review of its Use as an Adjuvant Anticancer Therapy in Early Breast Cancer , 2017, Drugs.

[45]  N. Radojević,et al.  Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving fertility. , 2015, European review for medical and pharmacological sciences.

[46]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[47]  A. Hopkins.  Network pharmacology , 2007, Nature Biotechnology.