Polysaccharide extracted from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja enhanced stress resistance in Caenorhabditis elegans via skn-1 and hsf-1

Cyclocarya paliurus polysaccharide (CPP) has many beneficial biological activities. Although the antioxidant activity of CPP is well-known, the stress tolerance and underlying mechanism of the activities of CPP have not been determined in vivo. In this study, we applied the emerging model of Caenorhabditis elegans (C. elegans) to observe that CPP imparted stronger resistance to stress than the positive control Astragalus polysaccharide (H2O2- and paraquat-induced oxidative stress, as well as heat stress) without threatening the growth and reproduction of worms. Further studies found that CPP-treated worms had a strong antioxidant defense system that downregulated peroxidation products (ROS, MDA, NEFAs and GSSG) and upregulated antioxidant enzymes and nonenzymatic activities (SOD, CAT, GSH-Px and GSH). The CPP-treated worms also exhibited improved physiological functions, such as inhibition of age pigment and improvement of lifespan, mobility and neuroprotection. Further exploration of the mechanism of action of CPP treatment suggested that increased resistance to CPP might activate stress-inducible genes (sod-3, sod-5, ctl-1, ctl-2, hsp-16.1 and hsp-16.2) via skn-1 and hsf-1, rather than daf-16. These findings suggest that CPP may have health benefits for humans.