关键词:Parkinson's disease,Drug Discovery,Bushen-Yizhi formula,neuroinflammation

Abstract:Objective：Parkinson's disease (PD) is the second largest neurodegenerative disease following Alzheimer's disease (AD), which associated with aging. There are many similarities in pathology and pathogenesis, even in the TCM theory understanding, so we can learn from each other in the process of drug discovery. The clinical results showed that Bushen-Yizhi formula (BSYZ) could effectively improve the neurological function score of senile dementia patients and had a better anti-dementia effect. Further pharmacological studies showed that BSYZ had neuroprotective effects, such as anti-inflammatory, anti-oxidation, anti-apoptosis and neurotrophic effects. In this study, the therapeutic effect of BSYZ on PD was evaluated in vivo and in vivo, and its molecular mechanism was discussed in order to expand the scope of application of BSYZ and to provide strategies for drug discovery of related neurodegenerative diseases. Methods：C57BL/6 mice were injected intraperitoneally with MPTP to construct a PD mouse model. BSYZ (1.46, 2.92, 5.84g/ Kg) was administered for two weeks, and the positive control group was given a NSAID,piroxicam (12.5 mg/ Kg) . After 1 week of pretreatment, MPTP was used to construct a PD mouse model. The mice were subjected to Rotation test on days 1, 3 and 5, 6th day. and the movement coordination and exercise ability of the drug on PD mice were observed on theThe number of TH - positive cells, Iba1 and CD68 - labeled microglial cells in SNpc region were observed by immunofluorescence to observe the proliferation and activation of microglial cells and GFAP - labeled astrocytes .Western blotting was used to detect the nuclear transfer of NLRP3, Caspase-1, ASC, pro-IL-1β, IL-1β and NF-κB in the midbrain. Results： 1. BSYZ could significantly improve the expression of MPTP model mice in the experiment of fatigue and Y-maze, increase the number of neurons in SNpc region and the positive expression of TH protein. 2. BSYZ significantly inhibited the number of Iba1/CD68-positive microglial cells in MPTP-model mice and decreased the number of GFAP-positive astrocytes. 3. BSYZ significantly inhibited the expression of NLRP3-associated protein in BV2 microglial cells induced by LPS+ATP and inhibited the nuclear transfer of NF-κB. Conclusion： BSYZ can effectively relieve the motor dysfunction of PD model mice, improve the damage of dopaminergic neurons, inhibit the proliferation and activation of microglial cells and astrocytes, and have good anti-MPTP -induced neuroinflammation and neuroinflammation mediated by nuclear transfer of NF-κB. The results show that BSYZ has a good prospect of anti - Parkinson's disease and provides valuable drug discovery strategies for the related neurodegenerative diseases.

Key words:Parkinson's disease,Drug Discovery,Bushen-Yizhi formula,neuroinflammation