Polyphenol-Loaded Plant Extracellular Vesicles: A New Approach to Combat AGEs-Induced Neurotoxicity via the Microbiota-Gut-Brain Axis

Excessive dietary intake of advanced glycation end products (AGEs) is a potential risk factor for neurodegenerative diseases (NDDs). The underlying mechanism may involve AGEs-induced impairment of intestinal barrier and disturbance of gut microbiota homeostasis, which in turn triggers neuroinflammation and oxidative stress via the microbiota-gut-brain (MGB) axis. Plant extracellular vesicles (PEVs), as natural nanocarriers, can not only enhance the bioavailability of polyphenols but also, in synergy with polyphenols, exhibit antioxidant, anti-inflammatory, and gut-microenvironment-modulating properties. This review summarizes and discusses the potential and mechanisms by which PEVs-polyphenols delivery systems may mitigate AGEs-related neurotoxicity by preserving MGB axis function, thereby providing a theoretical foundation for the development of prospective intervention strategies in this field.