title: Icariin has synergistic effects with methylprednisolone to ameliorate EAE via modulating HPA function, promoting anti-inflammatory and anti-apoptotic effects.
abstract: BACKGROUND
  High-dose methylprednisolone (MP) is a clinically recommended therapeutic regimen for Multiple Sclerosis (MS), whereas some dreadful complications induced by it remain inevitable. Studies implied that estrogens might play neuroprotective and anti-inflammatory roles in EAE and MS and promote glucocorticoid efficacy. Icariin (ICA), a primary active component of Epimedium extracts, also possesses neuroprotective and estrogen-like effects with less adverse complication than estrogen. However, rare study focuses ICA's effects on MS or EAE.
  
  
  OBJECTIVE
  Our purpose is to determine whether ICA has synergistic effects with MP in treating EAE and explore the possible mechanisms.
  
  
  METHODS
  C57BL/6 EAE mice were received different dose of ICA combined with MP and single MP treatment. Then, the clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT), Adrenocorticotropic Hormone (ACTH) concentrations were analyzed. Western blot and Flow Cytometry were used to investigate the expression of glucocorticoid receptor (GR) and cell apoptosis.
  
  
  RESULTS
  ICA has cooperative effects with MP in decreasing serum IL-17 and CORT concentrations, up-regulating the expression of GR in cerebral white matter and attenuating the cell apoptosis in spinal cord, especially high-dose ICA combined with MP.
  
  
  CONCLUSIONS
  ICA has synergistic effects with MP to ameliorate EAE via modulating hypothalamic-pituitary-adrenal (HPA) function, promoting anti-inflammatory and anti-apoptotic effects. ICA could be considered as a promising therapeutic option for MS.
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University No. 19 Nonglinxia Road, Guangzhou 510080, People's Republic of China.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Neurology, The Third Hospital of Wuhan No. 241 Peng Liuyang Road, Wuhan 430060, People's Republic of China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Deng
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University No. 19 Nonglinxia Road, 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 No. 19 Nonglinxia Road, Guangzhou 510080, People's Republic of China.
authors.forename: Quanxi
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University No. 19 Nonglinxia Road, 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 No. 19 Nonglinxia Road, 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 No. 19 Nonglinxia Road, 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 No. 19 Nonglinxia Road, Guangzhou 510080, People's Republic of China.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Peng
keywords: Icariin; experimental autoimmune encephalomyelitis; hypothalamic-pituitary-adrenal; methylprednisolone; multiple sclerosis