Extracellular vesicles: A new frontier in deciphering the mechanisms of traditional Chinese medicine

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles that mediate intercellular communication and hold significant promise as therapeutic agents, drug delivery vehicles, and biomarkers. This review systematically explores the bidirectional interplay between EVs and Traditional Chinese Medicine (TCM). We first summarize the unique bioactivity and therapeutic potential of Chinese herbal medicine-derived EVs (CHM-EVs), which retain plant-specific components and demonstrate anti-inflammatory, antioxidant, and tissue-protective effects. We critically expand the scope beyond the prevailing discourse on EVs' intrinsic mechanisms to investigate two significant emerging paradigms We examine EVs as innovative delivery platforms for TCM bioactive compounds, demonstrating how EVs enhance solubility, stability, and targeted delivery of challenging components to amplify therapeutic efficacy. Concurrently, we explore how TCM itself modulates endogenous EVs. Active ingredients within TCM formulations exert therapeutic effects by regulating host EV biogenesis, secretion, cargo composition, and bioactivity, as evidenced in diseases ranging from nephropathy to inflammation. We further evaluate challenges in CHM-EVs standardization (isolation, characterization, nomenclature), biosafety, and clinical translation. By integrating these perspectives, this review provides a panoramic overview of how EVs bridge TCM theory with modern mechanistic research, offering innovative strategies for advancing TCM modernization and EV-based therapeutics.