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Background: Epimedium sagittatum is a traditional Chinese herb normally which is used to treat the osteoporosis, cardiovascular dysfunction, and to improve neurological and sexual function in China, Korea and Japan. 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.

Titel:	Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways.
Autor/in / Beteiligte Person:	Chen, WF ; Wu, L ; Du, ZR ; Chen, L ; Xu, AL ; Chen, XH ; Teng, JJ ; Wong, MS
Link:	Zum Volltext
Zeitschrift:	Phytomedicine : international journal of phytotherapy and phytopharmacology, Jg. 25 (2017-02-15), S. 93
Veröffentlichung:	Stuttgart : Urban & Fischer Verlag ; <i>Original Publication</i>: Stuttgart ; New York : G. Fischer, c1994-, 2017
Medientyp:	academicJournal
ISSN:	1618-095X (electronic)
DOI:	10.1016/j.phymed.2016.12.017
Schlagwort:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Animals Chromones pharmacology Corpus Striatum metabolism Disease Models, Animal Dopamine metabolism Dopaminergic Neurons drug effects Dopaminergic Neurons metabolism Drugs, Chinese Herbal pharmacology Drugs, Chinese Herbal therapeutic use Enzyme Inhibitors pharmacology Epimedium chemistry Female Mice, Inbred C57BL Morpholines pharmacology Neuroprotective Agents therapeutic use Parkinson Disease drug therapy Parkinson Disease etiology Phosphorylation drug effects Phytotherapy Signal Transduction drug effects Tyrosine 3-Monooxygenase metabolism Corpus Striatum drug effects Flavonoids pharmacology MAP Kinase Signaling System drug effects Neuroprotective Agents pharmacology Parkinson Disease metabolism Phosphatidylinositol 3-Kinase metabolism Proto-Oncogene Proteins c-akt metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Phytomedicine] 2017 Feb 15; Vol. 25, pp. 93-99. <i>Date of Electronic Publication: </i>2016 Dec 29. MeSH Terms: Corpus Striatum / drug effects ; Flavonoids / pharmacology ; MAP Kinase Signaling System / drug effects ; Neuroprotective Agents / pharmacology ; Parkinson Disease / metabolism ; Phosphatidylinositol 3-Kinase / metabolism ; Proto-Oncogene Proteins c-akt / *metabolism ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Chromones / pharmacology ; Corpus Striatum / metabolism ; Disease Models, Animal ; Dopamine / metabolism ; Dopaminergic Neurons / drug effects ; Dopaminergic Neurons / metabolism ; Drugs, Chinese Herbal / pharmacology ; Drugs, Chinese Herbal / therapeutic use ; Enzyme Inhibitors / pharmacology ; Epimedium / chemistry ; Female ; Mice, Inbred C57BL ; Morpholines / pharmacology ; Neuroprotective Agents / therapeutic use ; Parkinson Disease / drug therapy ; Parkinson Disease / etiology ; Phosphorylation / drug effects ; Phytotherapy ; Signal Transduction / drug effects ; Tyrosine 3-Monooxygenase / metabolism Contributed Indexing: Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Dopamine; Icariin; Mitogen-activated protein kinase kinase; Parkinson's disease; Phosphatidylinositol 3-kinase Substance Nomenclature: 0 (Chromones) ; 0 (Drugs, Chinese Herbal) ; 0 (Enzyme Inhibitors) ; 0 (Flavonoids) ; 0 (Morpholines) ; 0 (Neuroprotective Agents) ; 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) ; 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) ; EC 1.14.16.2 (Tyrosine 3-Monooxygenase) ; EC 2.7.1.137 (Phosphatidylinositol 3-Kinase) ; EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) ; SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) ; VNM47R2QSQ (icariin) ; VTD58H1Z2X (Dopamine) Entry Date(s): Date Created: 20170214 Date Completed: 20170517 Latest Revision: 20181202 Update Code: 20231215

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