Küpeli Akkol Esra, Karatoprak Gökçe Şeker, Dumlupınar Berrak, Bahadır Acıkara Özlem, Arıcı Reyhan, Yücel Çiğdem, Aynal Leyli Can, Sobarzo Sánchez Eduardo
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara 06330, Türkiye.
Department of Pharmacognosy, Faculty of Pharmacy, Erciyes University, Kayseri 38039, Türkiye.
Molecules. 2025 Apr 29;30(9):1982. doi: 10.3390/molecules30091982.
This review covers preclinical studies of stilbene derivative compounds (both natural and synthetic) with potential preventive and therapeutic effects against Alzheimer's disease (AD). AD is a worldwide neurodegenerative disease characterized by the destruction of nerve cells in the brain and the loss of cognitive function due to aging. Stilbenes are a unique class of natural phenolic compounds distinguished by a C6-C2-C6 (1,2-diphenylethylene) structure and two aromatic rings connected by an ethylene bridge. Stilbenes' distinct features make them an intriguing subject for pharmacological research and development. Several preclinical studies have suggested that stilbenes may have neuroprotective effects by reducing Aβ generation and oligomerization, enhancing Aβ clearance, and regulating tau neuropathology through the prevention of aberrant tau phosphorylation and aggregation, as well as scavenging reactive oxygen species. Synthetic stilbene derivatives also target multiple pathways involved in neuroprotection and have demonstrated promising biological activity in vitro. However, some properties of stilbenes, such as sensitivity to physiological conditions, low solubility, poor permeability, instability, and low bioavailability, limit their usefulness in clinical applications. To address this issue, current investigations have developed new drug delivery systems based on stilbene derivative molecules. This review aims to shed light on the development of next-generation treatment strategies by examining in detail the role of stilbenes in Alzheimer's pathophysiology and their therapeutic potential.
本综述涵盖了对具有预防和治疗阿尔茨海默病（AD）潜在作用的芪类衍生物化合物（包括天然和合成的）的临床前研究。AD是一种全球性神经退行性疾病，其特征是大脑中的神经细胞遭到破坏以及因衰老导致认知功能丧失。芪类是一类独特的天然酚类化合物，其特征结构为C6-C2-C6（1,2-二苯乙烯），由一个乙烯桥连接两个芳香环。芪类的独特特性使其成为药理学研发中一个引人关注的课题。多项临床前研究表明，芪类可能具有神经保护作用，可通过减少Aβ生成和寡聚化、增强Aβ清除以及通过防止异常的tau磷酸化和聚集来调节tau神经病理学，还能清除活性氧。合成芪类衍生物也靶向参与神经保护的多种途径，并在体外显示出有前景的生物活性。然而，芪类的一些特性，如对生理条件敏感、溶解度低、通透性差、不稳定以及生物利用度低，限制了它们在临床应用中的效用。为解决这一问题，目前的研究基于芪类衍生物分子开发了新的药物递送系统。本综述旨在通过详细研究芪类在阿尔茨海默病病理生理学中的作用及其治疗潜力，为下一代治疗策略的发展提供启示。
