Jayatunga Dona P W, Hone Eugene, Fernando W M A D Binosha, Garg Manohar L, Verdile Giuseppe, Martins Ralph N
Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Cooperative Research Centre for Mental Health, Carlton, VIC, Australia.
Front Aging Neurosci. 2022 Feb 21;13:781468. doi: 10.3389/fnagi.2021.781468. eCollection 2021.
Evidence to date suggests the consumption of food rich in bioactive compounds, such as polyphenols, flavonoids, omega-3 fatty acids may potentially minimize age-related cognitive decline. For neurodegenerative diseases, such as Alzheimer's disease (AD), which do not yet have definitive treatments, the focus has shifted toward using alternative approaches, including prevention strategies rather than disease reversal. In this aspect, certain nutraceuticals have become promising compounds due to their neuroprotective properties. Moreover, the multifaceted AD pathophysiology encourages the use of multiple bioactive components that may be synergistic in their protective roles when combined. The objective of the present study was to determine mechanisms of action underlying the inhibition of Aβ-induced toxicity by a previously determined, three-compound nutraceutical combination DLU for AD. experiments were carried out in human neuroblastoma BE(2)-M17 cells for levels of ROS, ATP mitophagy, and mitobiogenesis. The component compounds luteolin (LUT), DHA, and urolithin A (UA) were independently protective of mitochondria; however, the DLU preceded its single constituents in all assays used. Overall, it indicated that DLU had potent inhibitory effects against Aβ-induced toxicity through protecting mitochondria. These mitoprotective activities included minimizing oxidative stress, increasing ATP and inducing mitophagy and mitobiogenesis. However, this synergistic nutraceutical combination warrants further investigations in other and AD models to confirm its potential to be used as a preventative therapy for AD.
迄今为止的证据表明，食用富含生物活性化合物的食物，如多酚、类黄酮、ω-3脂肪酸，可能会潜在地减少与年龄相关的认知衰退。对于神经退行性疾病，如尚无确切治疗方法的阿尔茨海默病（AD），重点已转向使用替代方法，包括预防策略而非疾病逆转。在这方面，某些营养保健品因其神经保护特性而成为有前景的化合物。此外，AD多方面的病理生理学促使人们使用多种生物活性成分，这些成分在组合时可能在其保护作用中具有协同作用。本研究的目的是确定先前确定的用于AD的三种化合物营养保健品组合DLU抑制Aβ诱导毒性作用的潜在机制。在人神经母细胞瘤BE(2)-M17细胞中进行了关于活性氧水平、ATP、线粒体自噬和线粒体生物发生的实验。成分化合物木犀草素（LUT）、二十二碳六烯酸（DHA）和尿石素A（UA）各自对线粒体具有保护作用；然而，在所有使用的检测中，DLU都优于其单一成分。总体而言，这表明DLU通过保护线粒体对Aβ诱导的毒性具有强大的抑制作用。这些线粒体保护活性包括将氧化应激降至最低、增加ATP以及诱导线粒体自噬和线粒体生物发生。然而，这种具有协同作用的营养保健品组合有待在其他AD模型中进一步研究，以确认其作为AD预防疗法的潜力。
