Jujube Polysaccharide Promotes Neuroprotection and Longevity in <i>Caenorhabditis elegans</i> Through Oxidative Stress Resistance and Stress-Response Signaling.

Parkinson's disease (PD) involves oxidative stress, proteotoxic aggregation, and neurotransmitter dysfunction, yet current therapies remain largely symptomatic. This study investigated whether Jujube polysaccharides (ZJP), a food-derived polysaccharide, confer neuroprotective and anti-aging benefits in <i>Caenorhabditis elegans</i>. ZJP was characterized for physicochemical features, antioxidant capacity, and in vivo safety. Effects were evaluated in wild-type N2 and PD models by measuring lifespan, locomotion, pharyngeal pumping, chemotaxis, α-syn::YFP fluorescence intensity, dopaminergic neuron integrity, adenosine triphosphate (ATP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and lipofuscin. Stress resilience was assessed under heat (37 °C) and H₂O₂ exposure. RT-qPCR profiled genes related to stress responses and neurotransmission. ZJP showed no detectable toxicity at tested doses. ZJP extended mean lifespan in N2 (10.3-14.1%) and NL5901 (9.1%), improved locomotion, pharyngeal pumping, and chemotaxis, reduced lipofuscin (26.8-50.6%), and increased survival under heat (23.6%) and oxidative stress (38.1%). In PD models, ZJP reduced α-syn::YFP fluorescence by up to 54.9%, protected dopaminergic neurons, and increased ATP. It also lowered ROS and MDA levels while raising SOD and CAT activities. Gene expression changes were associated with enhanced oxidative stress resistance and with altered expression of genes involved in SKN-1/DAF-16-related stress-response signaling. These findings provide preliminary evidence that ZJP may promote longevity, stress resilience, and neuroprotection in <i>C. elegans</i> models of PD, supporting its potential as a candidate for further investigation in neuroprotection.