Abstract
Parkinson disease (PD) is an age-related neurodegenerative disease, which is associated with the loss of dopaminergic neurons (DA neurons) in the substantia nigra pars compacta (SNpc), and neuroinflammation may lead to the occurrence of PD. Wuzi Yanzong Pill (WYP) has demonstrated neuroprotective and anti-inflammatory properties, but its molecular mechanism of action is still unclear. In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and LPS-mediated BV2 microglia to explore WYP intervention, anti-inflammatory effect and molecular mechanism in vivo and in vitro. The results showed that oral administration of WYP in MPTP-induced PD mice for 2 weeks ameliorated abnormal motor dysfunction, attenuated the loss of TH + neurons in SNpc, protected dopaminergic neurons, and inhibited the activation of microglia in MPTP-induced PD mice and LPS-stimulated BV2 cell. Meanwhile, WYP intervention inhibited the expression of IL-6, TNF-α, Pro-IL-1β, IL-1β, Pro-IL-18, IL-18 and enhanced the expression of IL-10 in the SNpc of PD mice. Simultaneously, WYP intervention inhibited the expression of NLRP3 inflammasome, accompanied by the decrease of the TLR4/MyD88/NF-κB pathway. However, the exact target and interaction of WYP on NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway still needs to be further investigated.
Highlights
WYP treatment increased the number of DA neurons in SNpc, improved the behavioral performance of MPTP-induced PD mice, and inhibited the activation of microglia and astrocytes.
WYP inhibits inflammatory factors in PD mice and BV2 cells.
WYP intervention inhibits NLRP3 inflammasome expression while decreasing TLR4/MyD88/NF-κB pathway.
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Data Availability
Data are available from the corresponding author upon request.
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Acknowledgements
We would like to deeply appreciate all authors who performed all eligible studies which have been included in the present paper.
Funding
This study was supported by the National Natural Science Foundation of China (No.81703978), the National Young Qihuang Scholars Training Program(No.〔2022〕256), the Key National Science and Technology Cooperation Project of Shanxi Province(No.202204041101002), the Outstanding Youth Talents Program of Shanxi Province (No.〔2019〕35), the Natural Science Foundation of Shanxi Province (No.20210302124293), the Research Project supported by Shanxi Scholarship Council of China (No.2021 − 142), the Key science and technology R&D project of Jinzhong(No.Y213004), the Science and Technology Innovation Ability Cultivation Project, Shanxi University of Chinese Medicine (No.2020PY-JC-03, No.2021PY-QN-03, No.2022PY-TH-16, No.2022TD1013).
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Tao Pan, Qi Xiao and Hui-Jie Fan carried out the studies and drafted the manuscript. Lei Xu, Shao-Chen Qin and Li-Xia Yang participated in collecting data, performed the statistical analysis. Zhi Chai, Cun-gen Ma and Bo Zhang participated in its design. Bao-guo Xiao and Xiao-ming Jin participated in polishing the language and interpretation of data. All authors read and approved the final manuscript.
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Pan, T., Xiao, Q., Fan, HJ. et al. Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation. Metab Brain Dis 38, 2211–2222 (2023). https://doi.org/10.1007/s11011-023-01266-8
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DOI: https://doi.org/10.1007/s11011-023-01266-8