Wuzi Yanzong Pill relieves MPTP-induced motor dysfunction and neuron loss by inhibiting NLRP3 inflammasome-mediated neuroinflammation

• Published in: Metabolic brain disease 2023-10, Vol.38 (7), p.2211-2222
• Main Authors: Pan, Tao, Xiao, Qi, Fan, Hui-Jie, Xu, Lei, Qin, Shao-Chen, Yang, Li-Xia, Jin, Xiao-ming, Xiao, Bao-Guo, Zhang, Bo, Ma, Cun-Gen, Chai, Zhi
• Format: Article
• Language: English
• Subjects: Age; Anti-inflammatory agents; Astrocytes; Biochemistry; Biomedical and Life Sciences; Biomedicine; Dopamine receptors; IL-1β; Inflammasomes; Inflammation; Interleukin 18; Lipopolysaccharides; Metabolic Diseases; Microglia; Molecular modelling; Movement disorders; MPTP; MyD88 protein; Neurodegenerative diseases; Neurology; Neurons; Neuroprotection; Neurosciences; NF-κB protein; Oncology; Oral administration; Original Article; Parkinson's disease; Substantia nigra; TLR4 protein; Toll-like receptors; Tumor necrosis factor-α
• ISSN: 0885-7490; 1573-7365; 1573-7365
• DOI: 10.1007/s11011-023-01266-8

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.