ZJP-2, a novel wild jujube polysaccharide, enhances longevity, cognitive function, and mitigates oxidative stress via mitochondrial regulation in Caenorhabditis elegans.

Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, drives aging and age related functional decline. Natural polysaccharides from medicinal plants are promising interventions against oxidative stress related disorders. This study examined the protective effects of a novel polysaccharide (ZJP-2) isolated from wild jujube (Ziziphus jujuba Mill. var. spinosa) against stress induced physiological deterioration in Caenorhabditis elegans. Using lipopolysaccharide exposure, heat shock, and oxidative stress models, we assessed ZJP-2 effects on lifespan, health span, antioxidant capacity, and stress response pathways. ZJP-2 (0.25-1 mg/mL) showed no toxicity and did not inhibit Escherichia coli OP50 growth. Treatment significantly improved locomotor activity, pharyngeal pumping, and reproductive capacity. The optimal dose increased average lifespan by 42.03% and reduced intestinal lipofuscin accumulation by 52.89%. Under heat stress (37 °C), ZJP-2 enhanced thermotolerance and improved survival under oxidative stress. Intracellular ROS levels decreased in a dose dependent manner, accompanied by reductions in malondialdehyde and increases in superoxide dismutase, catalase, and glutathione activities. Gene expression analysis revealed modulation of antioxidant and mitochondrial-associated genes, along with p38 MAPK-associated genes. ZJP-2 also promoted activation of the longevity associated transcription factor daf-16. These findings demonstrate that ZJP-2 enhances stress resistance, reduces oxidative damage, and promotes a healthy lifespan, highlighting its potential as a natural bioactive compound to mitigate stress related aging.