Assessment of the treatment effect of baicalein on a model of Parkinsonian tremor and elucidation of the mechanism

摘要

Aims: The aim of the present study is to evaluate the effects of baicalein on the 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinsonian tremor and elucidate the potential mechanism. Main methods: Adult male Sprague-Dawley rats were subjected to Parkinsonian tremor by 6-OHDA-medial forebrain bundle (MFB) injection. Baicalein (100, 200 and 400 mg/kg) was administrated by gavage once daily, for 1 week. The anti-tremor effect of baicalein on a model of Parkinsonian tremor was examined. Dopamine (DA), glutamate (GLu) and gamma-aminobutyric acid (GABA) levels in basal ganglia were determined by HPLC-ECD. Cytochrome oxidase subunit I (COI) mRNA expression in subthalamic nucleus (STN) was assessed by real-time RT-PCR. GABA transaminase (GABA-T) and glutamine synthetase (GS) protein expression in basal ganglia were tested by immunostaining. Effects of baicalein on [Ca 2 +]i induced by GLu were tested in primary cultured mesencephalic neurons. Key findings: Baicalein significantly attenuated muscle tremor of PD rats. The metabolic balance between GLu and GABA was modulated by baicalein treatment. It was found that treatment with baicalein inhibited the STN's COI mRNA expression in experimental PD. In rat primary mesencephalic cultures, baicalein inhibited significantly GLu-induced intracellular calcium [Ca 2 +]i increase. Significance: These results suggest that baicalein plays a neuromodulatory role in balancing GABA and GLu neurotransmitter in basal ganglia, and might be a promising candidate for the treatment of tremor-dominant type of idiopathic Parkinson's disease.