Neuroprotective effects of Korean medicinal plants in animal model of Parkinson's disease

Abstract

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and is the most prevalent movement disorder.1 Inflammation-mediated cell death is thought to contribute to dopaminergic cell death.2,3 In this study, extract of some Korean medicinal and edible plants such as Daphne genkwa Siebold. & Zucc. [Thymelaeaceae] were found to attenuate motor dysfunction in 6-OHDA-induced Parkinson's disease rat model and exhibited a protective effect against 6-OHDA-induced dopaminergic neuronal cell death. Two active compounds, genkwanine N (1) and yuanhuacin (2) were isolated through bioactivity-guided fractionation from the extract and their chemical structures were identified by NMR and MS analyses. The compounds reduced the expression of proinflammatory genes including interleukin-1β (IL-1β) and interleukin-6 (IL-6) in microglia and prevented 6-OHDA-induced neuronal cell death. Importantly, in the 6-OHDA rat model of Parkinson's disease, oral administration of yuanhuacin (0.5 mg/kg/day) for 2 weeks significantly improved behavioral deficits and reduced tyrosine hydroxylase (TH)-positive dopaminergic neuron death induced by 6-OHDA injection. Additionally, microglia activation in dorsal striatum was inhibited, suggesting anti-parkinson effects of the compounds are related to their anti-inflammatory activity. These results suggest that the extract and the compounds could be promising candidates for the treatment of Parkinson's disease.