Stilbenes Against Alzheimer's Disease: A Comprehensive Review of Preclinical Studies of Natural and Synthetic Compounds Combined with the Contributions of Developed Nanodrug Delivery Systems.

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.