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.