Targeting glial modulation: molecular mechanisms of Polygonatum in neurological disorders

Neurological disorders arise from interconnected pathological processes, including oxidative stress, neuroinflammation, mitochondrial dysfunction, impaired proteostasis, synaptic injury and blood brain barrier disruption. Increasing evidence indicates that glial cells are not passive bystanders in these diseases, but central regulators of neuroimmune balance, metabolic support, myelin integrity and tissue repair. Polygonatum spp., a traditional medicinal and edible plant, contains diverse bioactive constituents, including polysaccharides, steroidal saponins and flavonoids, which exhibit multi-target neuroprotective activities. In this Review, we summarize current evidence linking Polygonatum and its active compounds to the modulation of glial function and neuronal survival. Polygonatum polysaccharides appear to suppress microglial overactivation, attenuate TLR4/NF-κB and NLRP3 inflammatory signalling, restore redox homeostasis through NRF2-related pathways, and reduce lipid peroxidation and ferroptosis. In parallel, Polygonatum-derived compounds may support mitochondrial function, protein homeostasis, synaptic plasticity and neurotransmitter balance, thereby improving pathological outcomes in models of Alzheimer's disease, Parkinson's disease, cerebral ischaemia, depression and sleep disturbance. Evidence for direct effects on oligodendrocytes, astrocytes, oligodendrocyte precursor cells and the neurovascular unit remains limited but suggests an important area for future investigation. Standardized botanical sources, extraction procedures, pharmacokinetic analyses and high-quality clinical studies will be essential to define the therapeutic potential of Polygonatum-based interventions for neurological diseases.