Rezaee Nasim, Hone Eugene, Sohrabi Hamid R, Johnson Stuart, Zhong Leizhou, Chatur Prakhar, Gunzburg Stuart, Martins Ralph N, Fernando W M A D Binosha
Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.
Department of Biomedical Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Foods. 2024 May 30;13(11):1716. doi: 10.3390/foods13111716.
Sorghum grain contains high levels and a diverse profile of polyphenols (PPs), which are antioxidants known to reduce oxidative stress when consumed in the diet. Oxidative stress leading to amyloid-β (Aβ) aggregation, neurotoxicity, and mitochondrial dysfunction is implicated in the pathogenesis of Alzheimer's disease (AD). Thus, PPs have gained attention as possible therapeutic agents for combating AD. This study aimed to (a) quantify the phenolic compounds (PP) and antioxidant capacities in extracts from six different varieties of sorghum grain and (b) investigate whether these PP extracts exhibit any protective effects on human neuroblastoma (BE(2)-M17) cells against Aβ- and tau-induced toxicity, Aβ aggregation, mitochondrial dysfunction, and reactive oxygen species (ROS) induced by Aβ and tert-butyl hydroperoxide (TBHP). PP and antioxidant capacity were quantified using chemical assays. Aβ- and tau-induced toxicity was determined using the 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTS) assay. The thioflavin T (Th-T) assay assessed anti-Aβ aggregation. The dichlorodihydrofluorescein diacetate (DCFDA) assay determined the levels of general ROS and the MitoSOX assay determined the levels of mitochondrial superoxide. Sorghum varieties Shawaya short black-1 and IS1311C possessed the highest levels of total phenolics, total flavonoids, and antioxidant capacity, and sorghum varieties differed significantly in their profile of individual PPs. All extracts significantly increased cell viability compared to the control (minus extract). Variety QL33 (at 2000 µg sorghum flour equivalents/mL) showed the strongest protective effect with a 28% reduction in Aβ-toxicity cell death. The extracts of all sorghum varieties significantly reduced Aβ aggregation. All extracts except that from variety B923296 demonstrated a significant ( ≤ 0.05) downregulation of Aβ-induced and TBHP-induced ROS and mitochondrial superoxide relative to the control (minus extract) in a dose- and variety-dependent manner. We have demonstrated for the first time that sorghum polyphenolic extracts show promising neuroprotective effects against AD, which indicates the potential of sorghum foods to exert a similar beneficial property in the human diet. However, further analysis in other cellular models and in vivo is needed to confirm these effects.
高粱籽粒含有高水平且种类多样的多酚（PPs），这些多酚是抗氧化剂，已知在饮食中摄入时可减轻氧化应激。导致淀粉样β蛋白（Aβ）聚集、神经毒性和线粒体功能障碍的氧化应激与阿尔茨海默病（AD）的发病机制有关。因此，多酚作为对抗AD的潜在治疗剂受到了关注。本研究旨在：（a）量化六种不同高粱籽粒品种提取物中的酚类化合物（PP）和抗氧化能力；（b）研究这些PP提取物是否对人神经母细胞瘤（BE(2)-M17）细胞具有任何保护作用，以抵抗Aβ和tau诱导的毒性、Aβ聚集、线粒体功能障碍以及由Aβ和叔丁基过氧化氢（TBHP）诱导的活性氧（ROS）。使用化学分析方法对PP和抗氧化能力进行量化。使用3-(4,5-二甲基噻唑-2-基)-2,5-二甲基四氮唑溴盐（MTS）分析方法测定Aβ和tau诱导的毒性。硫黄素T（Th-T）分析方法评估抗Aβ聚集能力。二氯二氢荧光素二乙酸酯（DCFDA）分析方法测定总ROS水平，MitoSOX分析方法测定线粒体超氧化物水平。高粱品种Shawaya short black-1和IS1311C的总酚、总黄酮含量以及抗氧化能力最高，不同高粱品种的单个PPs谱存在显著差异。与对照组（无提取物）相比，所有提取物均显著提高了细胞活力。QL33品种（在2000μg高粱粉当量/mL时）显示出最强的保护作用，Aβ毒性细胞死亡减少了28%。所有高粱品种的提取物均显著降低了Aβ聚集。除B923296品种的提取物外，所有提取物均以剂量和品种依赖性方式相对于对照组（无提取物）显著（≤0.05）下调了Aβ诱导和TBHP诱导的ROS以及线粒体超氧化物水平。我们首次证明高粱多酚提取物对AD具有有前景的神经保护作用，这表明高粱食品在人类饮食中具有发挥类似有益特性的潜力。然而，需要在其他细胞模型和体内进行进一步分析以证实这些作用。
