Morin exerts neuroprotective actions in Parkinson disease models in vitro and in vivo.
OBJECTIVE
To investigate the neuroprotective effects of morin on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced apoptosis in neuronal differentiated PC12 cells as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease (PD).


METHODS
PC12 cells were challenged with MPP(+) in the presence or absence of morin. Cell viability was determined using MTT assay. Cell apoptosis was measured using flow cytometry. Generation of reactive oxygen species (ROS) was assayed using fluorescence assay. In an MPTP mouse model of PD, behavioral deficits, striatal dopamine content, and number of dopaminergic neurons were measured.


RESULTS
MPP(+) induced apoptosis and ROS formation in PC12 cells. Concomitant treatment with morin (5-50 mumol/L) significantly attenuated the loss of cell viability and apoptosis when compared with MPP(+) treatment alone. Morin also attenuated ROS formation induced by MPP(+). MPTP induced permanent behavioral deficits and nigrostriatal lesions in mice. When administered prior to MPTP, morin (20 to 100 mg/kg) attenuated behavioral deficits, dopaminergic neuronal death and striatal dopamine depletion in the MPTP mouse model.


CONCLUSIONS
The findings suggest that morin has neuroprotective actions both in vitro and in vivo, and may provide a novel therapeutic agent for the treatment of PD and other neurodegenerative diseases.
Zhang
Zhen-tao
ZT
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China. zhangzhentao104@yahoo.com.cn
Cao
Xue-bing
XB
Xiong
Nian
N
Wang
Hong-cai
HC
Huang
Jin-sha
JS
Sun
Sheng-gang
SG
Wang
Tao
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D047309:Flavones
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000978:Antiparkinson Agents; D004298:Dopamine; D005419:Flavonoids; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C008548:morin; D047309:Flavones