The Therapeutic Potential of TCM Polysaccharides in Neurological Disorders

This review systematically evaluates the interactions between traditional Chinese medicine (TCM) polysaccharides and the blood-brain barrier (BBB), positioning BBB modulation as a central mechanistic framework to explain their neurotherapeutic potential. Unlike disease-specific prior works, it identifies BBB dysfunction as a unifying pathological bottleneck in central nervous system (CNS) disorders, offering a cohesive lens to interpret these polysaccharides' multitarget actions. We synthesize evidence on their structural characteristics and bioactivities, focusing on the regulation of tight junction (TJ) proteins, NVU homeostasis, and key signaling pathways. This synthesis elucidates their potential mechanisms in maintaining NVU homeostasis and modulating BBB permeability. Critical limitations are highlighted, including overreliance on preclinical models and the lack of direct evidence for BBB translocation and causal mechanisms. The review also discusses the therapeutic potential of TCM polysaccharides in preclinical models of stroke, AD, and PD, while evaluating current advances in extraction and purification technologies, pharmacokinetic characterization, and emerging nano-delivery strategies. Despite the promising findings, significant challenges persist-including structural heterogeneity, batch-to-batch variability, insufficient pharmacokinetic data, and substantial translational barriers. Collectively, this review aims to provide a systematic and forward-looking reference framework for future mechanistic investigations and translational development of TCM polysaccharides in BBB-related neurological disorders.