Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
Department of Neurology, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, India.
Neuromolecular Med. 2019 Mar;21(1):42-53. doi: 10.1007/s12017-018-08521-7. Epub 2019 Jan 14.
Parkinson's disease (PD), a neurodegenerative central nervous system disorder, is characterised by progressive loss of nigrostriatal neurons in basal ganglia. Previous studies regarding PD have suggested the role of oxidative stress along with neuroinflammation in neurodegeneration. Accordingly, our study explore the anti-inflammatory activity of Tinospora cordifolia aqueous extract (TCAE) in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)-intoxicated Parkinsonian mouse model. MPTP-intoxicated mice showed significant behavioral and biochemical abnormalities which were effectively reversed by TCAE. It is evident that TCAE inhibits the MPTP-intoxicated Nuclear factor-κB (NF-κB) activation and its associated pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) from immunohistochemistry and Western blot analysis. In MPTP-intoxicated mice, microglial and astroglial-specific inflammatory markers, ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP), respectively were increased while were significantly reduced in TCAE treatment. Expression of pro-inflammatory cytokine genes, TNF-α, Interleukin-12 (IL-12) and Interleukin-1β (IL-1β) were found to be upregulated in MPTP-intoxicated mice, whereas TCAE treatment restored their levels. Additionally, anti-inflammatory factor Interleukin-10 (IL-10) gene was found to be downregulated in MPTP-intoxicated mice which were significantly restored by TCAE treatment. Tyrosine hydroxylase (TH) expression was reduced in MPTP-intoxicated mice, while its expression was significantly increased in TCAE-treated group. Our result strongly suggests that T. cordifolia protects dopaminergic neurons by suppressing neuroinflammation in MPTP-induced Parkinsonian mouse model.
帕金森病(PD)是一种神经退行性中枢神经系统疾病,其特征是基底神经节中的黑质纹状体神经元进行性丧失。以前的 PD 研究表明,氧化应激与神经炎症在神经退行性变中起作用。因此,我们的研究探索了三叶鬼针草水提取物(TCAE)在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)中毒性帕金森病小鼠模型中的抗炎活性。MPTP 中毒的小鼠表现出明显的行为和生化异常,这些异常可被 TCAE 有效逆转。显然,TCAE 抑制了 MPTP 中毒核因子-κB(NF-κB)的激活及其相关促炎细胞因子肿瘤坏死因子-α(TNF-α)的激活,这可从免疫组织化学和 Western blot 分析中得到证明。在 MPTP 中毒的小鼠中,小胶质细胞和星形胶质细胞特异性炎症标志物,即离子钙结合接头分子 1(Iba1)和胶质纤维酸性蛋白(GFAP)分别增加,而在 TCAE 治疗中则明显减少。促炎细胞因子基因 TNF-α、白细胞介素-12(IL-12)和白细胞介素-1β(IL-1β)的表达在 MPTP 中毒的小鼠中被发现上调,而 TCAE 治疗则恢复了它们的水平。此外,抗炎因子白细胞介素-10(IL-10)基因在 MPTP 中毒的小鼠中被发现下调,而 TCAE 治疗则显著恢复了其水平。TH 表达在 MPTP 中毒的小鼠中降低,而在 TCAE 治疗组中则显著增加。我们的结果强烈表明,三叶鬼针草通过抑制 MPTP 诱导的帕金森病小鼠模型中的神经炎症来保护多巴胺能神经元。