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一种生物可利用姜黄素制剂对阿尔茨海默病病理的影响:神经炎症的潜在风险。

The effects of a bioavailable curcumin formulation on Alzheimer's disease pathologies: A potential risk for neuroinflammation.

作者信息

Cade Shaun, Prestidge Clive, Zhou Xin-Fu, Bobrovskaya Larisa

机构信息

Health and Biomedical Innovation, Clinical and Health Sciences University of South Australia Adelaide South Australia Australia.

Center for Pharmaceutical Innovation, Clinical and Health Sciences University of South Australia Adelaide South Australia Australia.

出版信息

Ibrain. 2024 Dec 11;10(4):500-518. doi: 10.1002/ibra.12187. eCollection 2024 Winter.

Abstract

Alzheimer's disease (AD) is a common cause of dementia characterized by the presence of two proteinaceous deposits in the brain. These pathologies may be a consequence of complex interactions between neurons and glia before the onset of cognitive impairments. Curcumin, a bioactive compound found in turmeric, is a promising candidate for AD because it alleviates neuropathologies in mouse models of the disease. Although its clinical efficacy has been hindered by low oral bioavailability, the development of new formulations may overcome this limitation. The purpose of this study was to determine the effects of a bioavailable curcumin formulation in a mouse model of AD. The formulation was administered to mice in drinking water after encapsulation into micelles using a previously validated method. A neuropathological assessment was performed to determine if it slows or alters the course of the disease. Cognitive performance was not included because it had already been assessed by a previous study. The bioavailable curcumin formulation was unable to alter the size or number of amyloid plaques in a transgenic mouse model. In addition, mechanisms that regulate amyloid beta production were unchanged, suggesting that the disease had not been altered. The number of reactive astrocytes in the hippocampus and dentate gyrus was not altered by curcumin. However, protein levels of glial fibrillary acidic protein were increased overall in the brain, suggesting that it may have aggravated neuroinflammation. Therefore, a higher dosage, despite its enhanced oral bioavailability, may have a potential risk for neuroinflammation.

摘要

阿尔茨海默病(AD)是痴呆的常见病因,其特征是大脑中存在两种蛋白质沉积物。这些病理状态可能是认知障碍发作前神经元与神经胶质细胞之间复杂相互作用的结果。姜黄素是姜黄中发现的一种生物活性化合物,因其能减轻该疾病小鼠模型中的神经病理状态,故而有望成为治疗AD的药物。尽管其临床疗效因口服生物利用度低而受到阻碍,但新制剂的研发可能会克服这一限制。本研究的目的是确定一种生物可利用的姜黄素制剂在AD小鼠模型中的作用。该制剂采用先前验证的方法包裹成胶束后通过饮用水给予小鼠。进行神经病理学评估以确定其是否减缓或改变疾病进程。未纳入认知表现评估,因为之前的一项研究已对其进行过评估。这种生物可利用的姜黄素制剂无法改变转基因小鼠模型中淀粉样斑块的大小或数量。此外,调节β淀粉样蛋白产生的机制未发生变化,这表明疾病未得到改变。姜黄素未改变海马体和齿状回中反应性星形胶质细胞的数量。然而,大脑中胶质纤维酸性蛋白的总体蛋白水平有所升高,这表明它可能加剧了神经炎症。因此,尽管其口服生物利用度有所提高,但较高剂量可能存在神经炎症的潜在风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2110/11649387/41aee21e31a7/IBRA-10-500-g005.jpg

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