Emerging Strategies for Alzheimer's Disease: Leveraging Flavonoid Derivatives for Early Diagnosis and Neuroprotection

Abstract

Alzheimer's disease (AD) is a prevalent chronic and progressive neurodegenerative disorder predominantly affecting the elderly population. The etiology of AD is multifaceted, and despite extensive research, effective therapeutic options remain limited. Flavonoids, a diverse class of naturally occurring small molecules, exhibit a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective properties, which may have significant therapeutic implications for AD. However, the clinical application of flavonoids is hindered by their low bioavailability and poor blood permeability across the blood-brain barrier. In response to these challenges, researchers have synthesized various multifunctional compounds derived from naturally active flavonoids, thereby enhancing the therapeutic potential of these agents. Furthermore, the privileged structure of flavonoids have facilitated their advancement in the diagnostic realm of AD. This review aims to elucidate the beneficial roles and therapeutic potential of flavonoids and their derivatives in the treatment and diagnosis of AD. We further evaluated the the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of 36 flavonoid derivatives with anti-AD activity, thereby informing the rational design of novel flavonoid-based candidates for Alzheimer's disease.