Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Nutr Neurosci. 2021 Feb;24(2):90-101. doi: 10.1080/1028415X.2019.1596613. Epub 2019 Mar 30.
An imbalance of free radicals and antioxidant defense systems in physiological processes can result in protein/DNA damage, inflammation, and cellular apoptosis leading to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Sesamin and sesamol, compounds derived from sesame seeds and oil, have been reported to exert various pharmacological effects, especially antioxidant activity. However, their molecular mechanisms against the oxidative stress induced by exogenous hydrogen peroxide (HO) remain to be elucidated. In this study, neuroprotective effects of sesamin and sesamol on HO-induced human neuroblastoma (SH-SY5Y) cell death and possible signaling pathways in the cells were explored. MTT assay and flow cytometry were conducted to determine cell viability and apoptotic profiles of neuronal cells treated with sesamin and sesamol. Carboxy-DCFDA assay was used to measure reactive oxygen species (ROS). Moreover, Western blot analysis was performed to investigate protein profiles associated with neuroprotection. Pretreatment of the cells with 1 µM of sesamin and sesamol remarkably reduced the SH-SY5Y cell death induced by 400 µM HO as well as the intracellular ROS production. Moreover, the molecular mechanisms underlying neuroprotection of the compounds were associated with activating SIRT1-SIRT3-FOXO3a expression, inhibiting BAX (proapoptotic protein), and upregulating BCL-2 (anti-apoptotic protein). The findings suggest that sesamin and sesamol are compounds that potentially protect neuronal cells against oxidative stress similar to that of the resveratrol, the reference compound. These antioxidants are thus of interest for further investigation in models of neuroprotection.
在生理过程中，自由基和抗氧化防御系统的失衡会导致蛋白质/DNA 损伤、炎症和细胞凋亡，从而导致神经退行性疾病，如阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）。芝麻素和芝麻酚是从芝麻种子和油中提取的化合物，据报道具有多种药理作用，特别是抗氧化活性。然而，它们对由外源性过氧化氢（HO）引起的氧化应激的分子机制仍有待阐明。在这项研究中，研究了芝麻素和芝麻酚对 HO 诱导的人神经母细胞瘤（SH-SY5Y）细胞死亡的神经保护作用及其在细胞中的可能信号通路。MTT 测定和流式细胞术用于确定用芝麻素和芝麻酚处理的神经元细胞的细胞活力和凋亡谱。Carboxy-DCFDA 测定用于测量活性氧（ROS）。此外，进行了 Western blot 分析以研究与神经保护相关的蛋白质谱。用 1μM 的芝麻素和芝麻酚预处理细胞可显著降低 400μM HO 诱导的 SH-SY5Y 细胞死亡以及细胞内 ROS 的产生。此外，这些化合物的神经保护的分子机制与激活 SIRT1-SIRT3-FOXO3a 表达、抑制 BAX（促凋亡蛋白）和上调 BCL-2（抗凋亡蛋白）有关。研究结果表明，芝麻素和芝麻酚是潜在的保护神经元细胞免受氧化应激的化合物，类似于参考化合物白藜芦醇。这些抗氧化剂因此引起了人们对神经保护模型中进一步研究的兴趣。
