Neuroprotective Effects of Herbal Butanol Extracts from Gynostemma pentaphyllum on the Exposure to Chronic Stress in a 6-Hydroxydopamine- Lesioned Rat Model of Parkinson's Disease Treated with or Without L-DOPA

Parkinson’s disease (PD), which is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, is accompanied by symptoms of muscular rigidity, bradykinesia, rest tremor, and loss of postural balance (Fearnley & Lees, 1991). Mitochondrial dysfunction by reactive oxygen species (ROS)-induced oxidative stress has also been suggested to be important in the loss of dopaminergic neurons in PD (Ozawa et al., 1990). Therefore, the degeneration of the dopaminergic nigrostriatal tracts in PD results in a corresponding decrease in the levels of dopamine and its metabolites, including 3,4dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and norepinephrine (Hornykiewicz, 1982). 3,4-Dihydroxyphenylalanine (L-DOPA), the precursor of dopamine, is the most prescribed therapy for the symptomatic relief of PD (Neil & David, 2008; Marsden, 1994). However, chronic prolonged therapy for PD with L-DOPA results in a loss of drug efficacy and irreversible adverse effects, and subsequently leads to the development of motor complications, such as fluctuation and dyskinesia (Jankovic, 2005). L-DOPA and dopamine can accelerate the degenerative process in the residual cells in patients with PD and induce oxidative stress-induced neurotoxicity by generating ROS in primary dopaminergic neurons and dopaminergic cell lines (Cheng et al., 1996). ROS generation leads to neuronal damage and apoptotic or non-apoptotic cell death (Walkinshaw & Waters, 1995). Dopaminergic neurons are in a perpetual state of oxidative stress, and this imbalance may lead to reduced levels of endogenous antioxidants (Merad-Boudia, 1998). In addition, chronic treatment with L-DOPA