The Effect of Polysaccharides and Saponins from Polygonatum kingianum on Cognitive Dysfunction in an AlCl3-Induced Alzheimer’s Disease Zebrafish Model

Polygonatum kingianum (PK), a plant with established medicinal and nutritional applications, has shown potential neuroprotective activity in Alzheimer’s disease (AD). Nevertheless, the effects of its major bioactive fractions remain unclear. This study examined the neuroprotective effects of PK polysaccharides (PKPs) and saponins (PKSs) using an AlCl3-induced zebrafish model. Chemical analyses revealed that PKP was dominated by a low-molecular-weight fraction (1890 Da, 83.8%), whereas LC-MS analysis detected 13 tentatively identified steroidal saponins within PKS, including diosgenin. Furthermore, behavioral assessments demonstrated that both PKP and PKS improved locomotor and cognitive functions. PKP exhibited a stronger effect on the cholinergic system; its acetylcholinesterase (AChE) inhibitory activity at 60 μg/mL was comparable to that of donepezil under the experimental conditions. Histopathological analysis indicated that PKP showed a stronger effect in reducing neuronal apoptosis, resulting in a 68% reduction in the number of apoptotic cells. Conversely, PKS displayed a greater effect on amyloid pathology, reducing amyloid-beta (Aβ) aggregation by 62%. These findings suggest that PKP and PKS showed different neuroprotective profiles in the zebrafish model. Specifically, PKP was more closely associated with cholinergic regulation and neuronal survival, whereas PKS showed a stronger effect on Aβ aggregation. This study provides experimental support for the potential use of PK-derived fractions as food-derived bioactive components for alleviating AD-related pathological changes.