Zhisheng Wei1, Mengxia Wang2, Mingfan Hong1, Shengpeng Diao1, Aiqun Liu1, Yeqing Huang1, Qingyun Yu1, Zhongxing Peng1. 1. Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou 510080, People's Republic of China. 2. Intensive Care Unit, Guangdong No. 2 Provincial People's Hospital Guangzhou 510317, People's Republic of China.
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. CONCLUSION: 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.
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. CONCLUSION: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: Jeroen Melief; Stella J de Wit; Corbert G van Eden; Charlotte Teunissen; Jörg Hamann; Bernard M Uitdehaag; Dick Swaab; Inge Huitinga Journal: Acta Neuropathol Date: 2013-06-28 Impact factor: 17.088
Authors: Daniel K Crawford; Mario Mangiardi; Bingbing Song; Rhusheet Patel; Sienmi Du; Michael V Sofroniew; Rhonda R Voskuhl; Seema K Tiwari-Woodruff Journal: Brain Date: 2010-09-21 Impact factor: 13.501