Istituti Clinici Scientifici Maugeri IRCCS, Pavia, 27100, Italy.
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, Milano, 20126, Italy.
J Nanobiotechnology. 2024 Nov 17;22(1):718. doi: 10.1186/s12951-024-02897-4.
The global demographic shift towards an aging population is generating a rise in neurodegenerative conditions, with Alzheimer's disease (AD) as the most prominent problem. In this landscape, the use of natural supplements has garnered attention for their potential in dementia prevention. Curcumin (Cur), derived from Curcuma longa, has demonstrated promising pharmacological effects against AD by reducing the levels of inflammatory mediators. However, its clinical efficacy is hindered by poor solubility and bioavailability. Our study introduces the use of H-Ferritin nanocages (HFn) as a nanoformulation vehicle for Cur, aiming to enhance its therapeutic potential for AD. In this work, we characterized a nanoformulation of Cur in HFn (HFn-CUR) by evaluating its safety, stability, and its transport across the blood-brain barrier (BBB) in vitro. Moreover, we evaluated the efficacy of HFn-CUR by transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from both AD patients and healthy controls (HC), and by using the well-established 5xFAD mouse model of AD.
Our data show that HFn-CUR exhibits improved water dispersibility, is non-toxic, and can traverse the BBB. Regarding its activity on PBMCs from AD patients, HFn-CUR enhances cellular responses to inflammation and reduces RAGE-mediated stress. Studies on an AD mouse model demonstrate that HFn-CUR exhibits mild beneficial effects on cognitive performance. Moreover, it effectively reduces microgliosis and astrogliosis and in vivo in mouse, suggesting potential neuroprotective benefits.
Our data suggest that HFn-CUR is safe and effective in reducing inflammation in both in vitro and in vivo models of AD, supporting the need for further experiments to define its optimal use.
全球人口结构向老龄化转变，导致神经退行性疾病发病率上升，其中阿尔茨海默病（AD）最为突出。在此背景下，天然补充剂因其在预防痴呆方面的潜力而受到关注。姜黄素（Cur）来源于姜黄，通过降低炎症介质水平，显示出对 AD 的有前景的药理作用。然而，其临床疗效受到溶解度和生物利用度差的限制。我们的研究介绍了使用 H-铁蛋白纳米笼（HFn）作为姜黄素的纳米制剂载体，旨在增强其治疗 AD 的潜力。在这项工作中，我们通过评估其在体外的安全性、稳定性及其穿过血脑屏障（BBB）的能力，对 HFn 中的姜黄素纳米制剂（HFn-CUR）进行了表征。此外，我们通过对 AD 患者和健康对照者（HC）外周血单核细胞（PBMC）的转录组分析，以及使用经过充分验证的 5xFAD AD 小鼠模型，评估了 HFn-CUR 的疗效。
我们的数据表明，HFn-CUR 具有改善的水分散性、无毒性且能够穿透 BBB。关于其对 AD 患者 PBMC 的活性，HFn-CUR 增强了细胞对炎症的反应，并减少了 RAGE 介导的应激。在 AD 小鼠模型上的研究表明，HFn-CUR 对认知表现具有轻微的有益作用。此外，它还能有效减少小胶质细胞和星形胶质细胞的激活，在体内具有潜在的神经保护作用。
我们的数据表明，HFn-CUR 在减少 AD 的体外和体内模型中的炎症方面是安全有效的，这支持了进一步实验以确定其最佳用途的必要性。
