Isobavachalcone Attenuates MPTP-Induced Parkinson's Disease in Mice by Inhibition of Microglial Activation through NF-κB Pathway

被引:86
作者
Jing, Haoran [1 ,2 ]
Wang, Shaoxia [2 ]
Wang, Min [1 ]
Fu, Wenliang [1 ]
Zhang, Chao [1 ]
Xu, Donggang [1 ]
机构
[1] Beijing Inst Basic Med Sci, Lab Genome Engn, Beijing, Peoples R China
[2] Tianjin Univ Tradit Chinese Med, Tianjin Key Lab Chinese Med Pharmacol, Tianjin, Peoples R China
关键词
NEUROINFLAMMATION;
D O I
10.1371/journal.pone.0169560
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of beta-amyloid (A beta 42) deposited in hippocampus in Alzheimer's patients. Whether it has the therapeutic effect on Parkinson's disease, however, is unclear. In this study, we found that isobavachalcone could effectively remit Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), prolong the residence time of mice on Rota-rod and alleviate the neuronal necrosis. It also inhibited the over-activation of microglia, and decreased the expression of IL-6 and IL-1 beta in the brain of PD mice. In vitro, isobavachalcone could inhibit nuclear factor-kappaB (NF-kappa B) pathway through inhibiting the LPS-induced transfer of NF-kappa B subunit from cytoplasm to nucleus in BV-2 cells. Isobavachalcone decreased the LPS-induced oxidative stress and the expression of inflammatory cytokines, and provided a neuroprotective effect by antagonizing microglia-mediated inflammation. Our results indicated that isobavachalcone may be a candidated drug against Parkinson's disease with great clinical potential.
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页数:15
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