From Antioxidants to Multi-Target Therapeutics: The Emerging Role of Flavonoids in Neurodegenerative Diseases

Flavonoids represent a varied collection of polyphenolic compounds derived from plants, present in numerous food sources, including fruits, vegetables, tea, coffee, honey, and various medicinal plants. Historically, these compounds have garnered attention regarding their potential effects on brain health, a focus that has grown particularly urgent due to the escalating global prevalence of neurodegenerative disorders. Diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and other forms of cognitive decline associated with ageing now impact millions, highlighting the pressing demand for therapeutic approaches that are both safe and biologically relevant. A substantial body of empirical research indicates that flavonoids may interact with multiple pathways that influence neuronal sensitivity. Various subclasses of flavonoids appear to modulate oxidative homeostasis, inflammatory signaling, mitochondrial function, and synaptic communication. In a range of in vitro and in vivo investigations, these compounds have demonstrated the capacity to neutralize reactive oxygen species, regulate apoptotic and inflammatory pathways, and facilitate processes integral to neurogenesis and synaptic plasticity. Certain metabolites possess the ability to traverse the blood–brain barrier, suggesting a more profound interaction with neural tissue than initially believed. This chapter synthesizes preclinical and clinical data on prominent flavonoid subclasses, including flavanones, flavanols, flavones, flavonols, anthocyanins, and isoflavones, and explores how their structural characteristics may correlate with neuroprotective effects. The discussion extends to the principal barriers that hinder the transition of these compounds into clinical applications, including limited bioavailability, metabolic differences among individuals, dose-dependent effects, and the challenge of translating experimental outcomes to human contexts. Potential strategies aimed at enhancing their therapeutic profiles are also considered.