Central nervous system diseases are major causes of disability and death, with persistent activation of neuroinflammation and glial functional imbalance being one of the common pathological features. As important bioactive constituents of traditional Chinese medicine (TCM), TCM polysaccharides, possess multiple biological activities, including immunomodulatory, anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-regulating effects. They have shown potential neuroprotective effects in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression, cerebral ischemia-reperfusion injury, and other central nervous system diseases. Current evidence indicates that TCM polysaccharides can ameliorate aberrant glial responses and glia-mediated neuroinflammatory injury by regulating microglial activation and polarization, phagocytosis and pathological clearance, and autophagy-lipid droplet metabolism, maintaining astrocyte homeostasis, and promoting oligodendrocyte lineage differentiation and remyelination. The underlying mechanisms involve multiple signaling pathways, including nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), phosphatidylinositol-3-hydroxykinase (PI3K)/protein kinase B (Akt), etc. Overall, TCM polysaccharides exert multi-target and multi-level regulatory characteristics on glial cells, which constitutes an important mechanistic basis for timproving central nervous system diseases. Future studies should further strengthen polysaccharide structural characterization, target validation, and clinical translational research to provide evidence for elucidating its neuroprotective mechanism and promoting application development.

traditional Chinese medicine polysaccharides  /  glial cells  /  microglia  /  astrocytes  /  oligodendrocytes  /  neuroinflammation  /  central nervous system diseases