RA Reduces 6-hydroxydendrobine-induced Dopamine Neuron Degeneration In Rats

Parkinson's disease (PD) is the secondly most prevalent neurodegenerative disease just after Alzheimer's disease. Neuropathological hallmarks of the disease include the degeneration and loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent dopamine (DA) depletion in the striatum. The mechanisms underlying PD pathogenesis have not been revealed yet. Multiple factors might be involved, such as heredity, environmental factors, oxidative stress, inflammation, iron accumulation and cell apoptosis. So far, there is no effective medicine and therapeutics to prevent or invert progression of PD. Therefore it becomes a new research area to search for naturally highly-effective neuroprotective medicine.Rosmarinic acid (RA) is a naturally occurring polyphenolic compound firstly exacted from rosmarinius officinalis in 1958, which has a variety of biological functions including anti-inflammatory, anti-oxidative, free radical scavenging activities and so on. The aim of present study is to explore the neuroprotective effects of RA on dopaminergic neurons against PD, as well as the underlying mechanisms. In the present study, By a combination of high-performance liquid chromatograph electrochemical detection (HPLC-ECD), immunohistochemistry and semi-quantitative RT-PCR, the toxic effects of 6-hydroxydopamine (6-OHDA) on the SN-Str projection system were investigated. Effects of curcumin on 6-OHDA-mediated neurotoxic effects were further investigated. The results were as follows:1. After 6-OHDA lesions, the DA in the Str decreased compared with that of control, In the RA treatment group, the DA increased compared with that of 6-OHDA treatment group.2. The numbers of tyrosine hydroxylase (TH) positive neurons in the SN decreased after 6-OHDA lesions compared with that of control group. RA significantly inhibited 6-OHDA-induced decrease of the numbers of TH positive neurons.3. After 6-OHDA lesions, the numbers of iron-staining cells increased in the SN compared with that of control group. RA significantly inhibited 6-OHDA-induced increase of the numbers of iron-staining cells.4. RA protected against 6-hydroxydopamine-induced Motor dysfunction depletion in rats.5. RA protected against 6-hydroxydopamine-induced down-regulation of Bcl-2/Bax ratio.The results suggested that RA plays a neuroprotective role by ameliorating mitochondrial dysfunction against 6-ODHA-induced dopamine neuron, and suggest that RA has potential to be considered as an aid for prevention of Parkinson's disease.