Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson's Disease through NF-κB/pAKT Signaling Pathways.
Mucuna pruriens Protects against MPTP Intoxicated Neuroinflammation in Parkinson's Disease through NF-κB/pAKT Signaling Pathways.
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DOI：
10.3389/fnagi.2017.00421
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发表时间：
2017
影响因子：
4.8
通讯作者：
Singh SP
中科院分区：
文献类型：
--
作者：
Rai SN;Birla H;Singh SS;Zahra W;Patil RR;Jadhav JP;Gedda MR;Singh SP
迄今为止，用于治疗帕金森病（PD）的药物仅表现出症状缓解，除了无法预防神经退行性变外，还具有几种不良反应。神经炎症在PD的进展中起着重要作用，并且可以针对其有效治疗。研究人员认为，草药植物表现出抗炎和抗氧化特性，因此对人类健康有益。传统上，Mucuna pruriens（Mp）种子在印度用于保持男性生殖力。据报道，MP被用作具有神经保护特性的再生药物。本研究旨在探讨MP水提物（100 mg/kgbwt）对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）中毒小鼠神经炎症的影响以及参与PD进展的分子机制。在这项研究中，我们观察到显着的行为异常，除了降低抗氧化防御MPTP中毒小鼠。我们还观察到帕金森病小鼠的黑质丘脑部（SNpc）中的炎症参数如胶质纤维酸性蛋白、诱导型一氧化氮合酶、细胞间细胞粘附分子和肿瘤坏死因子α显著增加，而MP治疗显著降低了这些炎症参数。MP还抑制MPTP诱导的NF-κB活化，促进pAkt 1活性，进一步抑制多巴胺能神经元凋亡。此外，Mp还通过抑制脂质过氧化反应和亚硝酸盐水平，提高黑质纹状体区过氧化氢酶活性和GSH水平，表现出明显的抗氧化防御作用。MP还恢复了MPTP治疗小鼠的行为异常。此外，MP治疗显著增加帕金森病小鼠SNPC中酪氨酸羟化酶和多巴胺转运蛋白的免疫反应性。我们的Mp种子提取物的高效液相色谱分析表明，左旋多巴，没食子酸，植酸，槲皮素，和儿茶素等价物的主要成分，可能会导致神经保护在PD小鼠。我们的结果表明，含有L-DOPA和丰富的新型植物化学物质的混合物的MP提取物处理显著减轻MPTP通过NF-κB和pAkt途径诱导的神经毒性。由此观察到的结果表明，MP提取物可连续改善MPTP诱导的神经炎症，恢复PD小鼠的生化和行为异常，从而为其传统说法提供了科学依据。
Till date, drugs that have been used to manage Parkinson’s disease (PD) have only shown symptomatic relief with several adverse effects besides their inability to prevent neurodegeneration. Neuroinflammation plays an important role in the advancement of PD and can be targeted for its effective treatment. Researchers have suggested that herbal plants exhibiting the anti-inflammatory and anti-oxidant properties are therefore beneficial to human health. Conventionally, Mucuna pruriens (Mp) seeds are used for maintaining male virility in India. Reportedly, Mp is used as a rejuvenator drug having neuroprotective property. Our study aimed to investigate effects of aqueous extract of Mp (100 mg/kgbwt) on neuroinflammation, orally administered to mice intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as well as the molecular mechanism involved in the progression of PD. In this study, we have observed significant behavioral abnormalities beside decreased antioxidant defense in MPTP intoxicated mice. We have also observed significant increase in inflammatory parameters like Glial Fibrillary Acidic Protein, Inducible Nitric Oxide Synthase, Intercellular Cell Adhesion Molecule, and Tumor Necrosis Factor alpha in substantia nigra pars compacta (SNpc) of parkinsonian mice, while Mp treatment has notably reduced these inflammatory parameters. Mp also inhibited the MPTP induced activation of NF-κB and promoted pAkt1 activity which further prevented the apoptosis of the dopaminergic neurons. Moreover, Mp exhibited significant antioxidant defense by inhibiting the lipid peroxidation and nitrite level, and by improving catalase activity and enhancing GSH level in nigrostriatal region of mouse brain. Mp also recovered the behavioral abnormalities in MPTP treated mice. Additionally, Mp treatment considerably increased the immunoreactivity of Tyrosine Hydroxylase and Dopamine Transporter in SNpc of parkinsonian mice. Our high performance liquid chromatography analysis of the Mp seed extract have shown L-DOPA, gallic acid, phytic acid, quercetin, and catechin equivalents as the major components which might cause neuroprotection in PD mice. Our result suggested that Mp extract treatment containing L-DOPA and a mixture of rich novel phytochemicals significantly alleviates the MPTP induced neurotoxicity by NF-κB and pAkt pathway. The findings observed thereby indicate that Mp extract have suggestively ameliorated MPTP induced neuroinflammation, restored the biochemical and behavioral abnormalities in PD mouse and thus provided a scientific basis for its traditional claim.
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影响因子：
--
作者：
Costa LG;Garrick JM;Roquè PJ;Pellacani C
通讯作者：
Pellacani C
DOI：
10.1073/pnas.0711053105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Gorbatyuk, Oleg S.;Li, Shoudong;Muzyczka, Nicholas
通讯作者：
Muzyczka, Nicholas
黄芩素对 MPTP 神经毒性的神经保护作用：行为、生化和免疫组织化学特征
影响因子：
2.5
作者：
Cheng, Yinxia;He, Guorong;Du, Guanhua
通讯作者：
Du, Guanhua
影响因子：
2.3
作者：
Gao, Y.;Shang, C.;Buss, G. R.
通讯作者：
Buss, G. R.
影响因子：
5.3
作者：
Choi, DK;Pennathur, S;Przedborski, S
通讯作者：
Przedborski, S