Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Nutricosmeceuticals and Nutrigenomics Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia; Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Biomed Pharmacother. 2017 Nov;95:780-788. doi: 10.1016/j.biopha.2017.08.074. Epub 2017 Sep 8.
Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue.
虽然阿尔茨海默病（AD）的病因尚未明了，但有大量证据表明，由于异常的淀粉样前体蛋白（APP）加工和 Aβ代谢导致的过量淀粉样β（Aβ）积累是 AD 发病机制的关键过程。因此，目前正在积极寻求针对 APP 加工和 Aβ代谢的方法来治疗 AD。研究表明，高胆固醇和高脂肪饮食对认知功能有不良影响，并可能引发 AD 发病机制的开始。尽管黑种草种子（Nigella sativa）提取物及其主要活性化合物百里醌（TQ）具有神经药理学特性，但关于 AD 研究的记录有限。纳米乳液（NE）因其能够溶解非极性活性化合物而被用作药物递送系统，并广泛用于脑靶向研究。在此，研究了富含百里醌的纳米乳液（TQRFNE）、百里醌纳米乳液（TQNE）及其常规乳液对高脂肪/胆固醇饮食（HFCD）诱导的大鼠的影响。特别是，测量了大脑组织中的 Aβ生成；APP 加工、β-分泌酶 1（BACE1）、早老素 1（PSEN1）和早老素 2（PSEN2）的 γ-分泌酶、Aβ 降解；胰岛素降解酶（IDE）、Aβ 转运；低密度脂蛋白受体相关蛋白 1（LRP1）和晚期糖基化终产物受体（RAGE）。TQRFNE 降低了大脑 Aβ 片段长度 1-40 和 1-42（Aβ40 和 Aβ42）水平，从而减轻了 AD 的发病机制。这种减少可能是由于调节β-和γ-分泌酶活性，以及 Aβ 在大脑内外的降解和转运。研究结果表明了 TQRFNE 在应对高脂肪和高胆固醇饮食与 Aβ 生成、降解和转运相关的大鼠脑组织中的作用机制。
