Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways

Wen Fang Chen, Lin Wu, Zhong Rui Du, Lei Chen, Ai Li Xu, Xiao Han Chen, Ji Jun Teng, Man Sau Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

51 Citations (Scopus)

Abstract

Icariin is the major active ingredient in Epimedium sagittatum. In the present research, we examined the neuroprotective effects of icariin on dopaminergic neurons and the possible mechanisms in a mouse model of Parkinson's disease (PD). Methods Ovariectomized PD mice were treated with vehicle or icariin (3 days before MPTP injections) with or without the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or mitogen-activated protein kinase kinase (MEK) inhibitor PD98059. The dopamine (DA) content in the striatum was studied by HPLC. Western blot was used to determine the protein expressions of Bcl-2, Bax and Caspase 3 in the striatum. The numbers of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc) were assessed by immunohistochemistry. The activation of Akt and ERK by icariin were detected in doparminergic MES23.5 cells. Results Icariin pretreatment could ameliorate the decreased striatum DA content and the loss of TH-IR neurons in the SNpc induced by MPTP. The MPTP-induced changes of Bcl-2, Bax and caspase 3 protein expressions in the striatum could be reversed by icariin pretreatment. Blockade of PI3K/Akt or MEK/ERK signaling pathway by LY294002 or PD98059 could attenuate the increase of DA content in the striatum and TH-IR in the SNpc induced by icariin in PD mice model. Additionally, icariin treatment alone significantly induced the phosphorylation of Akt and ERK in a time dependent pattern in dopaminergic MES 23.5 cells. These effects were abolished by co-treatment with LY294002 or PD98059. Conclusion These data demonstrated that icariin has neuroprotective effect on dopaminergic neurons in PD mice model and the potential mechanisms might be related to PI3K/Akt and MEK/ERK pathways.
Original languageEnglish
Pages (from-to)93-99
Number of pages7
JournalPhytomedicine
Volume25
DOIs
Publication statusPublished - 15 Feb 2017

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine
  • Icariin
  • Mitogen-activated protein kinase kinase
  • Parkinson's disease
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine

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