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Naringin Exhibits Neuroprotection Against Rotenone-Induced Neurotoxicity in Experimental Rodents.
NeuroMolecular Medicine ( IF 3.5 ) Pub Date : 2020-01-08 , DOI: 10.1007/s12017-019-08590-2
Debapriya Garabadu 1 , Nidhi Agrawal 1
Affiliation  

Parkinson’s disease (PD) is a neurodegenerative disease that is accompanied with the loss of dopaminergic neurons in the substantia nigra pars compacta which subsequently leads to a reduction in the dopamine level in the striatum. The flavonoids are gaining critical attention in the management of PD due to the toxic effects of the synthetic drugs. Naringin, a potent flavonoid, exerts neuroprotective activity against experimental animal models of PD. It also exhibits protective activity against rotenone-induced neurotoxicity in cell line studies. Therefore, the present study was designed to evaluate the therapeutic potential of naringin against rotenone-induced animal model of PD. The rotenone was injected through intracerebroventricular route into substantia nigra pars compacta (SNpc) to induce PD-like manifestations in the male rats. The behavioral deficits of the animals due to dopaminergic toxicity were evaluated in actophotometer, OFT, bar catalepsy, narrow beam walk, rota-rod, grip strength and foot print analysis. Naringin-attenuated rotenone-induced behavioral abnormalities in the experimental rats. Further, naringin reduced the rotenone-induced dopaminergic toxicity in striatum and SNpc the animals. At the sub-cellular level, naringin attenuated the rotenone-induced decrease in the mitochondrial function, integrity and bioenergetics in the SNpc of the animals. Furthermore, naringin reduced the rotenone-induced mitochondria-dependent apoptosis in the rat SNpc. However, Trigonelline significantly abolished the therapeutic effects of naringin on behavioral, biochemical and molecular observations in rotenone-induced PD-like animals. These observations indicate that naringin may exert neuroprotective activity against rotenone-induced toxicity in the animals possibly through Nrf2-mediated pathway. Thus, it can be presumed that naringin could be an alternative option in the management of PD.

中文翻译:

柚皮苷在实验性啮齿动物中表现出针对鱼藤酮诱导的神经毒性的神经保护作用。

帕金森氏病(PD)是一种神经退行性疾病,伴有黑质致密部中多巴胺能神经元的丧失,继而导致纹状体中多巴胺水平降低。由于合成药物的毒性作用,类黄酮在PD的治疗中受到了关注。柚皮素是一种有效的类黄酮,对PD实验动物模型具有神经保护作用。在细胞系研究中,它还对鱼藤酮诱导的神经毒性具有保护作用。因此,本研究旨在评估柚皮苷对鱼藤酮诱导的PD动物模型的治疗潜力。将鱼藤酮通过脑室内途径注射到黑质致密性黑质(SNpc)中,以诱导雄性大鼠的PD样表现。在光度计,OFT,棒僵直症,窄束步,旋转杆,握力和脚印分析中评估了由于多巴胺能毒性引起的动物的行为缺陷。柚皮素减弱鱼藤酮诱导的实验大鼠行为异常。此外,柚皮苷减少了鱼藤酮诱导的动物纹状体和SNpc中的多巴胺能毒性。在亚细胞水平上,柚皮苷减弱了鱼藤酮诱导的动物SNpc中线粒体功能,完整性和生物能的下降。此外,柚皮苷减少了大鼠SNpc中鱼藤酮诱导的线粒体依赖性细胞凋亡。但是,曲古萘林显着取消了柚皮苷对鱼藤酮诱导的PD样动物的行为,生化和分子观察的治疗作用。这些观察结果表明柚皮苷可能通过Nrf2介导的途径对鱼藤酮诱导的动物毒性发挥神经保护作用。因此,可以推测,柚皮苷可能是PD管理中的另一种选择。
更新日期:2020-01-08
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