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α-Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone-Induced Rat Model of Parkinson’s disease
Biomolecules ( IF 4.8 ) Pub Date : 2020-10-08 , DOI: 10.3390/biom10101421
Hayate Javed 1 , M F Nagoor Meeran 2 , Sheikh Azimullah 2 , Lujain Bader Eddin 2 , Vivek Dhar Dwivedi 3 , Niraj Kumar Jha 4 , Shreesh Ojha 2, 5
Affiliation  

Rotenone (ROT), a plant-derived pesticide is a well-known environmental neurotoxin associated with causation of Parkinson’s disease (PD). ROT impairs mitochondrial dysfunction being mitochondrial complex-I (MC-1) inhibitor and perturbs antioxidant-oxidant balance that contributes to the onset and development of neuroinflammation and neurodegeneration in PD. Due to the scarcity of agents to prevent the disease or to cure or halt the progression of symptoms of PD, the focus is on exploring agents from naturally occurring dietary phytochemicals. Among numerous phytochemicals, α-Bisabolol (BSB), natural monocyclic sesquiterpene alcohol found in many ornamental flowers and edible plants garnered attention due to its potent pharmacological properties and therapeutic potential. Therefore, the present study investigated the neuroprotective effects of BSB in a rat model of ROT-induced dopaminergic neurodegeneration, a pathogenic feature of PD and underlying mechanism targeting oxidative stress, inflammation and apoptosis. BSB treatment significantly prevented ROT-induced loss of dopaminergic neurons and fibers in the substantia nigra and striatum respectively. BSB treatment also attenuated ROT-induced oxidative stress evidenced by inhibition of MDA formation and GSH depletion as well as improvement in antioxidant enzymes, SOD and catalase. BSB treatment also attenuated ROT-induced activation of the glial cells as well as the induction and release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and inflammatory mediators (iNOS and COX-2) in the striatum. In addition to countering oxidative stress and inflammation, BSB also attenuated apoptosis of dopaminergic neurons by attenuating downregulation of anti-apoptotic protein Bcl-2 and upregulation of pro-apoptotic proteins Bax, cleaved caspases-3 and 9. Further, BSB was observed to attenuate mitochondrial dysfunction by inhibiting mitochondrial lipid peroxidation, cytochrome-C release and reinstates the levels/activity of ATP and MC-I. The findings of the study demonstrate that BSB treatment salvaged dopaminergic neurons, attenuated microglia and astrocyte activation, induction of inflammatory mediators, proinflammatory cytokines and reduced the expression of pro-apoptotic markers. The in vitro study on ABTS radical revealed the antioxidant potential of BSB. The results of the present study are clearly suggestive of the neuroprotective effects of BSB through antioxidant, anti-inflammatory and anti-apoptotic properties in ROT-induced model of PD.

中文翻译:

α-红没药醇,一种膳食生物活性植物化学物质,通过调节鱼藤酮诱导的帕金森病大鼠模型中的氧化应激、神经炎症和细胞凋亡来减轻多巴胺能神经变性

鱼藤酮 (ROT) 是一种植物来源的杀虫剂,是一种众所周知的环境神经毒素,与帕金森病 (PD) 的病因有关。ROT 损害作为线粒体复合物-I (MC-1) 抑制剂的线粒体功能障碍,并扰乱抗氧化剂-氧化剂平衡,这有助于 PD 中神经炎症和神经变性的发生和发展。由于缺乏预防疾病或治愈或阻止 PD 症状进展的药物,重点是探索来自天然膳食植物化学物质的药物。在众多的植物化学物质中,α-红没药醇 (BSB),在许多观赏花卉和食用植物中发现的天然单环倍半萜醇因其强大的药理特性和治疗潜力而受到关注。所以,本研究调查了 BSB 在 ROT 诱导的多巴胺能神经变性大鼠模型中的神经保护作用,这是 PD 的一种致病特征,以及针对氧化应激、炎症和细胞凋亡的潜在机制。BSB 治疗分别显着防止了 ROT 诱导的黑质和纹状体中多巴胺能神经元和纤维的损失。BSB 处理还减弱了 ROT 诱导的氧化应激,这可以通过抑制 MDA 形成和 GSH 消耗以及抗氧化酶、SOD 和过氧化氢酶的改善来证明。BSB 治疗还减弱了 ROT 诱导的神经胶质细胞激活以及纹状体中促炎细胞因子(IL-1β、IL-6 和 TNF-α)和炎症介质(iNOS 和 COX-2)的诱导和释放。除了对抗氧化应激和炎症,BSB 还通过减弱抗凋亡蛋白 Bcl-2 的下调和促凋亡蛋白 Bax、cleaved caspase-3 和 9 的上调来减弱多巴胺能神经元的凋亡。 此外,观察到 BSB 通过抑制线粒体脂质过氧化、细胞色素来减轻线粒体功能障碍-C 释放并恢复 ATP 和 MC-I 的水平/活性。研究结果表明,BSB 治疗挽救了多巴胺能神经元,减弱了小胶质细胞和星形胶质细胞的活化,诱导了炎症介质、促炎细胞因子,并降低了促凋亡标志物的表达。ABTS 自由基的体外研究揭示了 BSB 的抗氧化潜力。本研究的结果清楚地表明 BSB 通过抗氧化剂的神经保护作用,
更新日期:2020-10-08
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