Plant extracellular vesicles as emerging neuroprotective agents for central nervous system disorders

BACKGROUND: Plant extracellular vesicles (PEVs) have emerged important roles in central nervous system (CNS) disorders. PEVs are nanoscale vesicles (30-150 nm) that mediate intercellular communication and exhibit unique therapeutic potential due to their natural biocompatibility, minimal immunogenicity, and ability to cross the blood-brain barrier (BBB). With increasing interest in neurotherapeutics, PEVs offer promising applications for CNS disorders by overcoming delivery barriers and reducing adverse effects associated with synthetic nanoparticles. AIM OF REVIEW: This review provides a comprehensive analysis of the role of PEVs in CNS disorders, focusing on their mechanisms of action, therapeutic potential, and advantages over mammalian extracellular vesicles (MEVs) and synthetic delivery systems. It also highlights emerging research, challenges, and future directions for their clinical translation. KEY SCIENTIFIC CONCEPTS OF REVIEW: PEVs, derived from fruits, vegetables, and medicinal plants, contain bioactive molecules such as proteins, lipids, microRNAs (miRNAs) and nucleic acids. These vesicles demonstrate the ability to traverse the BBB through receptor-mediated transport and membrane fusion, delivering therapeutic effects for CNS disorders, including neuroinflammation, ischemic stroke, and gliomas. Their pharmacological benefits stem from active metabolites, such as gingerols, alkaloids, and flavonoids, which modulate immune responses, maintain BBB integrity, and reduce neuronal apoptosis. Despite their advantages, challenges such as efficient extraction methods, standardization, and scalability remain obstacles to clinical application. Addressing these issues through advanced extraction techniques, improved characterization, and optimized drug loading strategies can enhance the clinical utility of PEVs.