Protective Effects of Gallic Acid on the MPTP-Mediated Dopaminergic Neurons Damage in Parkinson's Disease / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the neuroprotective effects of gallic acid in animal models of Parkinson's disease (PD) and its related molecular mechanisms. METHODS: Thirty-six mice were randomly divided into control group, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) group and gallic acid group. Mice in MPTP group and gallic acid group were given an intraperitoneal injection of 30 mg•kg-1 MPTP daily for 7 d. The mice in control group were given the same amount of normal saline at the same time. The mice in gallic acid group received oral administration of 200 mg•kg-1 gallic acid daily from the first day, gallic acid was administered continuously for 14 d, and mice in MPTP group and control group received the same amount of normal saline. After 7 d of drug administration, the behavioral function was evaluated by rod climbing test and suspension test. The expression of tyrosine hydroxylase(TH) in the substantia nigra and striatum were detected by immunohistochemistry. The number of apoptotic neurons in the substantia nigra were measured by TUNEL assay. SIRT3 mRNA levels were analyzed by qRT-PCR, and protein expression levels were detected by Western blot. RESULTS: Compared with the control group, the ability of motor coordination weakened, the TH expression levels decreased in the substantia nigra and striatum, the number of apoptotic neurons in the substantia nigra significantly increased, the SIRT3 mRNA and protein levels in the substantia nigra obviously declined, and the SOD2 protein expression also dramatically reduced in the MPTP group, the differences between the groups were all statistically significant (P<0.05). After treatment with gallic acid, the ability of motor coordination enhanced, the TH expression level elevated, the number of apoptotic neurons markedly reduced, SIRT3 mRNA and protein levels increased, and SOD2 protein expression also up-regulated in the gallic acid group. Compared with the MPTP group, the differences were all statistically significant (P<0.05). CONCLUSION: Gallic acid can improve the behavioral dysfunction and inhibit dopaminergic neurons damage in PD mice. The mechanism of action may be related to the up-regulation of SIRT3 gene expression.