title: Icariin exerts estrogen-like activity in ameliorating EAE via mediating estrogen receptor β, modulating HPA function and glucocorticoid receptor expression.
abstract: BACKGROUND
  Estrogen exerts neuroprotective and anti-inflammatory effects in EAE and multiple sclerosis (MS), but its clinical application is hindered due to side effects and risk of tumor. Phytoestrogen structurally or functionally mimics estrogen with fewer side effects than endogenous estrogen. Icariin (ICA), an active component of Epimedium extracts, demonstrates estrogen-like neuroprotective effects. However, it is unclear whether ICA is effective in EAE and what are the underlying mechanisms.
  
  
  OBJECTIVE
  To determine the therapeutic effects of ICA in EAE and explore the possible mechanisms.
  
  
  METHODS
  C57BL/6 EAE mice were treated with Diethylstilbestrol, different dose of ICA and mid-dose ICA combined with ICI 182780. The clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT) concentrations were then analyzed. Western blot were performed to investigate the expressions of glucocorticoid receptor (GR), estrogen receptor alpha (ERα) and ERβ in the cerebral white matter of EAE mice.
  
  
  RESULTS
  High dose ICA is equally effective in ameliorating neurological signs of EAE as estrogen. Estrogen and ICA has no effects on serum concentrations of IL-17 in EAE. While the CORT levels were decreased by ICA at mid or high doses, the expressions of GR, ERα and ERβ were up-regulated by estrogen or different doses of ICA in a dosedependent manner. Estrogen induced the elevation of ERα more markedly than ICA. In contrast, ICA at mid and high doses promoted ERβ more significantly than estrogen.
  
  
  CONCLUSIONS
  ICA exerts estrogen-like activity in ameliorating EAE via mediating ERβ, modulating HPA function and up-regulating the expression of GR in cerebral white matter. ICA may be a promising therapeutic option for MS.
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Intensive Care Unit, Guangdong No. 2 Provincial People's Hospital Guangzhou 510317, People's Republic of China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Mingfan
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Diao
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Aiqun
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Peng
keywords: Icariin; estrogen; estrogen receptor; experimental autoimmune encephalomyelitis; glucocorticoid receptor; hypothalamic-pituitary-adrenal; multiple sclerosis