School of Biomedical Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, NSW 2678, Australia.
Graham Centre for Agricultural Innovation (an alliance between Charles Sturt University and NSW Department of Primary Industries), Pugsley Place, Wagga Wagga, NSW 2795, Australia.
Nutrients. 2020 May 10;12(5):1366. doi: 10.3390/nu12051366.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unclear cause. It appears that multiple factors participate in the process of neuronal damage including oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on β-secretase (the enzyme that leads to the formation of Aβ), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells, was selected. Six taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Moreover, their neuroprotective effects on HO-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. and extracts lowered caspase activity. Exposure of SH-SY5Y cells to extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of the ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. and extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其病因尚不清楚。似乎有多种因素参与神经元损伤过程,包括氧化应激和脑内淀粉样蛋白β(Aβ)的积累。寻找治疗这种疾病的方法至关重要,因为目前的药物仅限于缓解症状和姑息治疗。本研究旨在研究薄荷提取物对 AD 发展中涉及的某些机制的影响。为了彻底研究机制,包括对β-分泌酶(导致 Aβ形成的酶)、Aβ聚集以及氧化应激和细胞凋亡途径的影响,选择神经元细胞模型 SH-SY5Y 细胞。研究了六种薄荷提取物对体外β-分泌酶(BACE)和 Aβ聚集抑制活性的影响。此外,通过半胱天冬酶活性评估了它们对 HO 诱导的 SH-SY5Y 细胞氧化应激和细胞凋亡的神经保护作用。通过实时 PCR 和 Western blot 分析对两种最有前途的提取物进行了研究,以确定它们对 SH-SY5Y 细胞信号通路的影响。所有薄荷提取物均具有很强的 BACE 抑制活性。 提取物显示出对 Aβ聚集的极好抑制作用,而其他提取物则显示出中等抑制作用。 和 提取物降低了半胱天冬酶活性。暴露于 提取物会导致促凋亡蛋白 Bax 的表达降低,抗凋亡蛋白 Bcl-xL 的表达升高,这可能是通过下调 ASK1-JNK 途径介导的。这些结果表明,薄荷提取物可以防止 Aβ的形成,如果已经形成,也可以防止其聚集。 和 提取物具有在细胞水平上抑制细胞凋亡的潜力。因此,薄荷提取物可以为 AD 的治疗方法提供有效的化合物来源。