title: Neuroprotective effects of ginkgetin against neuroinjury in Parkinson's disease model induced by MPTP via chelating iron.
abstract: Disruption of neuronal iron homeostasis and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Ginkgetin, a natural biflavonoid isolated from leaves of Ginkgo biloba L, has many known effects, including anti-inflammatory, anti-influenza virus, and anti-fungal activities, but its underlying mechanism of the neuroprotective effects in PD remains unclear. The present study utilized PD models induced by 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to explore the neuroprotective ability of ginkgetin in vivo and in vitro. Our results showed that ginkgetin could provide significant protection from MPP(+)-induced cell damage in vitro by decreasing the levels of intracellular reactive oxygen species and maintaining mitochondrial membrane potential. Meanwhile, ginkgetin dramatically inhibited cell apoptosis induced by MPP+ through the caspase-3 and Bcl2/Bax pathway. Moreover, ginkgetin significantly improved sensorimotor coordination in a mouse PD model induced by MPTP by dramatically inhibiting the decrease of tyrosine hydroxylase expression in the substantia nigra and superoxide dismutase activity in the striatum. Interestingly, ginkgetin could strongly chelate ferrous ion and thereby inhibit the increase of the intracellular labile iron pool through downregulating L-ferritin and upregulating transferrin receptor 1. These results indicate that the neuroprotective mechanism of ginkgetin against neurological injury induced by MPTP occurs via regulating iron homeostasis. Therefore, ginkgetin may provide neuroprotective therapy for PD and iron metabolism disorder related diseases.
authors.affiliation: Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University , Shijiazhuang, Hebei Province , China.
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Wang
authors.forename: M-Y
authors.initials: MY
authors.lastname: Wang
authors.forename: X-R
authors.initials: XR
authors.lastname: Fu
authors.lastname: Peng-Yu
authors.forename: G-F
authors.initials: GF
authors.lastname: Gao
authors.forename: Y-M
authors.initials: YM
authors.lastname: Fan
authors.forename: X-L
authors.initials: XL
authors.lastname: Duan
authors.forename: B-L
authors.initials: BL
authors.lastname: Zhao
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Chang
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Shi
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D015655:1-Methyl-4-phenylpyridinium / Q000009:adverse effects; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001052:Apoferritins / Q000378:metabolism; D017209:Apoptosis; D044946:Biflavonoids / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D020441:Ginkgo biloba; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000009:adverse effects; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D044946:Biflavonoids; C068126:CD71 antigen; D007502:Iron Chelating Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; C077458:ginkgetin; D001052:Apoferritins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium
keywords: Parkinson's disease; chelation; ginkgetin; iron homeostasis; oxidative stress