Pratiwi Reny, Nantasenamat Chanin, Ruankham Waralee, Suwanjang Wilasinee, Prachayasittikul Virapong, Prachayasittikul Supaluk, Phopin Kamonrat
Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Department of Medical Laboratory Technology, Faculty of Health Science, Setia Budi University, Surakarta, Indonesia.
Front Nutr. 2021 May 12;8:648995. doi: 10.3389/fnut.2021.648995. eCollection 2021.
Accumulating studies have confirmed that oxidative stress leads to the death of neuronal cells and is associated with the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Despite the compelling evidence, there is a drawback to the use of the antioxidant approach for AD treatment, partly due to limited blood-brain barrier (BBB) permeability. Phytosterol is known to exhibit BBB penetration and exerts various bioactivities such as antioxidant and anticancer effects, and displays a potential treatment for dyslipidemia, cardiovascular disease, and dementia. In this study, the protective effects of stigmasterol, a phytosterol compound, on cell death induced by hydrogen peroxide (HO) were examined using human neuronal cells (SH-SY5Y cells). MTT assay, reactive oxygen species measurement, mitochondrial membrane potential assay, apoptotic cell measurement, and protein expression profiles were performed to determine the neuroprotective properties of stigmasterol. HO exposure significantly increased the levels of reactive oxygen species (ROS) within the cells thereby inducing apoptosis. On the contrary, pretreatment with stigmasterol maintained ROS levels inside the cells and prevented oxidative stress-induced cell death. It was found that pre-incubation with stigmasterol also facilitated the upregulation of forkhead box O (FoxO) 3a, catalase, and anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) in the neurons. In addition, the expression levels of sirtuin 1 (SIRT1) were also increased while acetylated lysine levels were decreased, indicating that SIRT1 activity was stimulated by stigmasterol, and the result was comparable with the known SIRT1 activator, resveratrol. Taken together, these results suggest that stigmasterol could be potentially useful to alleviate neurodegeneration induced by oxidative stress.
越来越多的研究证实，氧化应激会导致神经元细胞死亡，并与包括阿尔茨海默病（AD）在内的神经退行性疾病的进展相关。尽管有确凿的证据，但使用抗氧化方法治疗AD存在一个缺点，部分原因是血脑屏障（BBB）通透性有限。已知植物甾醇具有BBB穿透性，并具有多种生物活性，如抗氧化和抗癌作用，对血脂异常、心血管疾病和痴呆症显示出潜在的治疗作用。在本研究中，使用人神经细胞（SH-SY5Y细胞）检测了植物甾醇化合物豆甾醇对过氧化氢（HO）诱导的细胞死亡的保护作用。进行MTT测定、活性氧测量、线粒体膜电位测定、凋亡细胞测量和蛋白质表达谱分析，以确定豆甾醇的神经保护特性。HO暴露显著增加了细胞内活性氧（ROS）水平，从而诱导细胞凋亡。相反，用豆甾醇预处理可维持细胞内ROS水平，并防止氧化应激诱导的细胞死亡。研究发现，用豆甾醇预孵育还促进了神经元中叉头框O（FoxO）3a、过氧化氢酶和抗凋亡蛋白B细胞淋巴瘤2（Bcl-2）的上调。此外，沉默调节蛋白1（SIRT1）的表达水平也增加，而乙酰化赖氨酸水平降低，表明豆甾醇刺激了SIRT1活性，结果与已知的SIRT1激活剂白藜芦醇相当。综上所述，这些结果表明豆甾醇可能有助于减轻氧化应激诱导的神经退行性变。
