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异长叶烯减轻鱼藤酮诱导的线粒体功能障碍、氧化应激和细胞凋亡。

Isolongifolene attenuates rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis.

作者信息

Balakrishnan Rengasamy, Elangovan Namasivayam, Mohankumar Thangavel, Nataraj Jegadeesan, Manivasagam Thamilarasan, Justin Thenmozhi Arokiasamy, Essa Mohamed Musthafa, Akbar Mohammed, Abdul Sattar Khan Mohammed

机构信息

Department of Biotechnology, School of Biosciences, Periyar University, Periyar Palkalai nagar, Salem-636011, Tamilnadu, India.

Department of Biotechnology, School of Biosciences, Periyar University, Periyar Palkalai nagar, Salem-636011, Tamilnadu, India,

出版信息

Front Biosci (Schol Ed). 2018 Jan 1;10(2):248-261. doi: 10.2741/s513.

Abstract

The present study was carried out to investigate the neuroprotective effects of isolongifolene (ILF), a tricyclic sesquiterpene of Murraya koenigii, against rotenone-induced mitochondrial dysfunction, oxidative stress and apoptosis in a cellular model. SH-SY5Y human neuroblastoma cells were divided into four experimental groups (control, rotenone (100 nM), ILF (10 microM) + rotenone (100 nanoM), ILF 10 microM alone treated) based on 3-(4, 5-dimethyl 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results of the present study showed that the ILF treatment significantly alleviated rotenone-induced cytotoxicity, oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. Moreover, ILF attenuated rotenone induced toxicity by down-regulating  Bax, caspases-3, 6, 8 and 9 expression and up-regulating of Bcl-2 expression. Furthermore regulation of p-P13K, p-AKT and p-GSK-3 beta expression by ILF, clearly confirmed its protective effects. Taken together, our results suggested that ILF attenuated rotenone-induced oxidative stress, mitochondrial dysfunction and apoptosis through the regulation of P13K/AKT/GSK-3 beta signaling pathways. However further pre-clinical studies are warranted in rodents to use ILF as a promising therapeutic agent for PD in future.

摘要

本研究旨在探讨九里香三环倍半萜异长叶烯(ILF)对鱼藤酮诱导的细胞模型中线粒体功能障碍、氧化应激和细胞凋亡的神经保护作用。基于3-(4,5-二甲基-2-噻唑基)-2,5-二苯基四氮唑溴盐(MTT)法,将SH-SY5Y人神经母细胞瘤细胞分为四个实验组(对照组、鱼藤酮(100 nM)组、ILF(10 μM)+鱼藤酮(100 nM)组、单独ILF 10 μM处理组)。本研究结果表明,ILF处理可显著减轻鱼藤酮诱导的SH-SY5Y细胞毒性、氧化应激和线粒体功能障碍。此外,ILF通过下调Bax、半胱天冬酶-3、6、8和9的表达以及上调Bcl-2的表达来减轻鱼藤酮诱导的毒性。此外,ILF对p-P13K、p-AKT和p-GSK-3β表达的调节,明确证实了其保护作用。综上所述,我们的结果表明,ILF通过调节P13K/AKT/GSK-3β信号通路减轻鱼藤酮诱导的氧化应激、线粒体功能障碍和细胞凋亡。然而,未来有必要在啮齿动物中进行进一步的临床前研究,以便将ILF用作治疗帕金森病的有前景的治疗药物

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