Protective effects of Chunghyuldan against ROS-mediated neuronal cell death in models of Parkinson's disease.
Previous reports have suggested that the herbal medicine Chunghyuldan (CHD, Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) has wide-ranging biological effects, including anti-hyperlipidaemic, anti-ischaemic, anti-inflammatory and antioxidant activities. Reactive oxygen species (ROS)-mediated mitochondrial dysfunction is thought to be one of the major pathological mechanisms responsible for Parkinson's disease (PD) and may underlie the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that is a hallmark of this disease. In this study, we examined the neuroprotective effects of CHD in PD models produced by treatment with neurotoxins that act via ROS-mediated mitochondrial dysfunction. In an in vitro PD model using 6-hydroxydopamine, CHD applied at concentrations of 10 and 100 μg/ml exhibited significant protective effects in PC12 cells by inhibiting intracellular ROS generation. CHD applied at 10 and 100 μg/ml also prevented 6-hydroxydopamine-induced mitochondrial depolarization and elevation of caspase-3 activity. At the same doses, CHD showed regulatory effects on the haem oxygenase-1 and gp91 phagocytic oxidase which have critical roles in generating ROS. In addition, CHD protected dopaminergic neurons in a primary mesencephalic culture against MPP+ neurotoxicity. In an in vivo PD model produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (20 mg/kg, 4 times, i.p.), co-administration of CHD (50 mg/kg, 5 days, p.o.) ameliorated PD-like behavioural symptoms (bradykinesia) and reduced dopaminergic neuronal damage in the SNpc and striatum as measured by immunocytochemistry. These results demonstrate the neuroprotective effects of CHD in PD models that are mediated through inhibition of ROS generation and associated mitochondrial dysfunction.
Kim
Hyo Geun
HG
College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Seoul, Korea.
Ju
Mi Sun
MS
Kim
Dong-Hyun
DH
Hong
Jongki
J
Cho
Seung-Hun
SH
Cho
Ki-Ho
KH
Park
Wansu
W
Lee
Eunjoo H
EH
Kim
Sun Yeou
SY
Oh
Myung Sook
MS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D016716:PC12 Cells; D010300:Parkinson Disease / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013378:Substantia Nigra / Q000473:pathology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C499382:Chunghyuldan; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; C040846:4-phenyl-1,2,3,6-tetrahydropyridine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D053148:Caspase 3; D004298:Dopamine