EFFECT OF ASTILBIN ON MPTP-INDUCED PARKINSONISM MICE BY MOTOR FUNCTIONS, NUMBER OF DOPAMINERGIC NEURONS, EXPRESSION OF TYROSINE HYDROXYLASE AND POTENTIAL SIGNALING PATHWAYS

Xinfu Lian, Yongjun Bai, Yuqian Jiang, Dongsheng Liu^*

Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine Zhuhai Branch, Zhuhai, PR China

Objective: To investigate the effect of astilbin on mice with MPTP-induced parkinsonism, in terms of motor functions, number of dopaminergic neurons, expression of tyrosine hydroxylase (TH) and potential signalling pathways. 

Methods: Seventy-two clean-grade healthy male C57BL/6 mice were randomly selected for adaptive feeding for 1 week. The mice were randomly divided into a control group, a model group and an astilbin group, with 24 mice in each group. A Parkinson mouse model was established and the control mice were housed normally without further treatment. Mice in the model group and the astilbin group were intraperitoneally injected with 30 mg/kg of MPTP once daily for 7 days. At the same time, mice in the astilbin group were intraperitoneally injected with 20 mg/kg of astilbin. All mice were sacrificed after the end of the experiment. The results of the climbing rod experiment and the suspension rope experiment of each group of mice were observed. Immunofluorescence was used to detect changes in the number of dopaminergic neurons. Western blotting was adopted to observe the number of TH-positive neurons and the expression of α-synuclein (α-syn) in the striata of each group, as well as the expression levels of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (Akt). The content of dopamine, serotonin and 5-hydroxyindoleacetic acid in the striata of each group was detected by high-performance liquid chromatography.

Results: Compared with the control group, the time required for the model group to climb down the cylinder was significantly prolonged, and the suspension time on the suspension rope was significantly shortened (P<0.05). The time required for mice in the astilbin group to climb down the cylinder was significantly shorter than that of the model group, and the suspension time on the suspension rope was significantly longer than that of the model group (P<0.05). Compared with the control group, the number of dopaminergic neurons in the model group was significantly decreased (P<0.05), and the number of dopaminergic neurons in the astilbin group was significantly higher than that in the model group (P<0.05). The content of dopamine, serotonin and 5-hydroxyindole acetic acid in the model group was significantly lower than that in the control group. The content of dopamine, serotonin and 5-hydroxyindole acetic acid in the astilbin group was significantly higher than that in the model group, and the difference was statistically significant (P<0.05). The number of TH-positive neurons in the striata of the model group was significantly decreased, and the expression level of α-syn was significantly increased (P<0.05). The number of TH-positive neurons in the striata of the astilbin group was significantly higher than that in the model group, and the expression level of α-syn was significantly lower than that in the model group (P<0.05). Compared with the control group, the expression levels of PI3K and Akt in the model group were significantly lower (P<0.05). Compared with the model group, the expression levels of PI3K and Akt in the mice of the astilbin group were significantly increased (P<0.05). 

Conclusions: Astilbin could improve the motor function of MPTP-induced Parkinson’s model mice by activating the PI3K/Akt pathway, reduce the loss of dopaminergic neurons, and inhibit the decrease of TH expression and the overexpression of α-syn. This shows that astilbin has obvious neuroprotective effects.