Quercetin alleviates 6-OHDA-caused apoptosis in SH-SY5Y cells.

IF 2.2 4区 医学 Q3 TOXICOLOGY Toxicology Research Pub Date : 2024-08-02 eCollection Date: 2024-08-01 DOI:10.1093/toxres/tfae117
Sourav Pakrashi, Joyeeta Chakraborty, Jaya Bandyopadhyay
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Abstract

Aim: This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells.

Materials and methods: Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye. Alteration of 6-OHDA-caused mitochondrial membrane potential and nuclear condensation was investigated with the help of rhodamine-123 and hoechest stain. Immunoblotting was performed to detect the expression level of 6-OHDA-caused alpha-synuclein (á-syn), Bcl-2 associated protein X (BAX), caspase 3, cleaved Poly ADP - ribose polymerase (PARP) and Bcell lymphoma 2 proteins (Bcl-2).

Result: Through MTT assay, quercetin was selected over myricetin and kaempferol to counter 6-OHDA-caused cell death. The research delves into unraveling the intricate mechanisms underlying 6-OHDA-induced neurotoxicity, encompassing alterations in cellular morphology, escalation of oxidative stress, perturbation in mitochondrial membrane potential, and nuclear condensation. Exposure to 6-OHDA is implicated in the upregulation of á-syn protein, contributing to the aggravation of neurotoxicity. Concurrently, 6-OHDA orchestrates the apoptotic pathway by upregulating the expression of proapoptotic proteins such as BAX, caspase 3, and PARP, while down regulating the expression of the Bcl-2, affirming its role in apoptosis induction. Quercetin demonstrated ability to attenuate the expression of á-syn in the presence of 6-OHDA-caused injury in SH-SY5Y cells.

Conclusion: Taken together, these findings collectively underscore the therapeutic potential of quercetin as a promising agent against neurotoxicity caused by 6-OHDA.

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槲皮素可减轻 6-OHDA 引起的 SH-SY5Y 细胞凋亡。
目的:本研究主要探讨多酚对 SH-SY5Y 细胞 6-OHDA 引起的神经毒性的潜在神经保护作用:采用MTT法分析6-OHDA对SH-SY5Y细胞的细胞毒性作用以及槲皮素、杨梅素和山奈酚的重要作用。使用 DCFDA 荧光染料测量了 6-OHDA 刺激的活性氧(ROS)的生成。利用罗丹明-123 和荷氏染色法研究了 6-OHDA 引起的线粒体膜电位和核凝聚的变化。免疫印迹法检测了6-OHDA引起的α-突触核蛋白(á-syn)、Bcl-2相关蛋白X(BAX)、Caspase 3、裂解聚ADP-核糖聚合酶(PARP)和B细胞淋巴瘤2蛋白(Bcl-2)的表达水平:结果:通过 MTT 试验,槲皮素被选中对抗 6-OHDA 引起的细胞死亡,而不是米黄素和山奈酚。研究揭示了6-OHDA诱导神经毒性的复杂机制,包括细胞形态改变、氧化应激升级、线粒体膜电位扰动和核凝结。暴露于 6-OHDA 会导致 á-syn 蛋白上调,从而加剧神经毒性。同时,6-OHDA 通过上调促凋亡蛋白(如 BAX、caspase 3 和 PARP)的表达来协调凋亡途径,同时下调 Bcl-2 的表达,从而肯定了其在凋亡诱导中的作用。槲皮素在6-OHDA导致的SH-SY5Y细胞损伤中能够减少á-syn的表达:综上所述,这些研究结果共同强调了槲皮素作为一种抗6-OHDA引起的神经毒性的药物所具有的治疗潜力。
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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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