title: Tanshinone IIA prevents the loss of nigrostriatal dopaminergic neurons by inhibiting NADPH oxidase and iNOS in the MPTP model of Parkinson's disease.
abstract: Tanshinone IIA is one of the major constituents of Salvia miltiorrhiza Bunge known as Danshen. Recent reports have shown that Tanshinone IIA has neuroprotective effects against cerebral ischemia/reperfusion injury and traumatic injury of the spinal cord in rats. However, whether Tanshinone IIA has any neuroprotective effect in Parkinson's disease remains unknown. In this study, we evaluated whether Tanshinone IIA promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and microglial activation as visualized by tyrosine hydroxylase and CD11b immunoreactivity. The results of Western blot and immunohistochemistry showed upregulation of NADPH oxidase and iNOS in the MPTP-treated substantia nigra pars compacta. Treatment with Tanshinone IIA prevented degeneration of nigrostriatal DA neurons and increased the level of striatal dopamine content. This neuroprotection afforded by Tanshinone IIA was associated with the suppression of microglial activation and reduced expression of NADPH oxidase and iNOS. The present findings show that Tanshinone IIA may possess anti-inflammatory and anti-oxidative properties and may have therapeutic value in the treatment of Parkinson's disease.
authors.affiliation: Medical Research Center, Jitang College of Hebei United University, Tangshan 063000, China. Electronic address: rendebo@gmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China. Electronic address: jpzyx@163.com.
authors.forename: Yu-xin
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: Hong-xia
authors.initials: HX
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: Fa-wei
authors.initials: FW
authors.lastname: Sun
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: Zuo-feng
authors.initials: ZF
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: ZifFeng
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: Cheng-yun
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Hebei United University, Tangshan 063000, China.
authors.forename: Dao-wen
authors.initials: DW
authors.lastname: Si
mesh_terms: D045784:Abietanes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D045784:Abietanes; D018696:Neuroprotective Agents; C021751:tanshinone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019255:NADPH Oxidases
keywords: MPTP; Microglia; NADPH oxidase; Parkinson's disease; Tanshinone IIA; iNOS