title: Anti-osteoporosis effect of Epimedium via an estrogen-like mechanism based on a system-level approach.
abstract: BACKGROUND
  Epimedium is a popular traditional herbal medicine worldwide that has long been used to relieve osteoporosis. The estrogenic properties of the herb are conferred by several phytoestrogens, such as flavonoids, lignans, and steroids. However, the poor understanding on the estrogen-like mechanism of Epimedium at the molecular and system levels limits the applications of this herb in osteoporosis treatment.
  
  
  METHODS
  In this study, systems pharmacology was established to investigate the relationship between Epimedium and estrogen against osteoporosis by integrating active component screening, drug-likeness evaluation, herb feature mapping, target prediction and validation, and network analysis.
  
  
  RESULTS
  A total of 77 active components that possessed similar structural features to estrogen as determined using herb feature mapping were selected from Epimedium by oral bioavailability prediction and drug-likeness evaluation. Twenty three osteoporosis-related targets were obtained from the active components of Epimedium as potential targets, 11 of which were common targets with estrogen. All osteoporosis-related targets were further mapped to compound-target and target-pathway networks. Results displayed that Epimedium can exert anti-osteoporosis effects by directly regulating the 11 estrogen-related targets and a set of target proteins on five estrogen-related pathways.
  
  
  CONCLUSIONS
  This study explained the estrogen-like mechanism of Epimedium in preventing and treating osteoporosis, and provided a new standpoint for exploring the traditional herbal medicine against osteoporosis.
authors.affiliation: School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Xu
authors.affiliation: School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China; Institute of Chemistry and Applications of Plant Resources, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China. Electronic address: dingyan_515@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China.
authors.forename: Baoyue
authors.initials: B
authors.lastname: Liu
authors.affiliation: Instrumental analysis center, Dalian Polytechnic University, Dalian 116034, PR China.
authors.forename: Zinong
authors.initials: Z
authors.lastname: Kou
authors.affiliation: Jiangsu Kanion Pharmaceutical Co. Ltd, Lianyungang 222001, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China; Institute of Chemistry and Applications of Plant Resources, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China. Electronic address: zhujingb@sina.com.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D016208:Databases, Factual; D034181:Epimedium / Q000737:chemistry*; D004967:Estrogens / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010024:Osteoporosis / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013597:Systems Analysis
chemical_list: D004967:Estrogens; D010936:Plant Extracts
keywords: (+)-Cycloolivil (PubChem CID: 5316262); (−)-Olivil (PubChem CID: 586733); Apigenin (PubChem CID: 5280443); Astragalin (PubChem CID: 5282102); Baohuoside VI (PubChem CID: 5488005); Baohuoside VII (PubChem CID: 5492427); Epimedin B (PubChem CID: 5748393); Epimedium; Icariin (PubChem CID: 5318997); Icaritin (PubChem CID: 5318980); Osteoporosis; Systems pharmacology; Yinyanghuo C (PubChem CID: 5315395); estrogen-like