Enhanced lifespan-extending effect of polydatin monolaurate and in vivo antioxidant activity of phenolic glycosides in Caenorhabditis elegans: evaluation and mechanism exploration

Phenolic glycoside monolaurate derivatives synthesized in our previous work exhibit significantly enhanced biological activities and improved intestinal absorption compared with their parent compounds. However, their in vivo functions and underlying mechanisms remain largely unclear, which limits their potential applications in nutrition and health. In this study, Caenorhabditis elegans was employed as an in vivo model to investigate the antioxidant and anti-aging activities of phenolic glycosides and their monolaurate derivatives. The results demonstrated that both phenolic glycosides and their monolaurate derivatives exhibited strong ROS-scavenging activity in C. elegans . Polydatin and polydatin monolaurate prolonged the mean lifespan of wild-type C. elegans by 10.5% and 14.9%, respectively, without exerting any adverse impacts on the body length or reproductive capacity of C. elegans . Both compounds reduced the accumulation of lipofuscin and malondialdehyde (MDA) in C. elegans , enhanced superoxide dismutase (SOD) activity, and strengthened the tolerance of C. elegans to oxidative stress, heat shock, and ultraviolet (UV)-induced damage. Furthermore, they effectively facilitated the nuclear translocation of the transcription factor DAF-16 in C. elegans . Gene expression profiling and mutant strain validation experiments confirmed that the lifespan-extending effects of these two compounds on wild-type C. elegans are mediated through the insulin/insulin-like growth factor 1 signaling (IIS) pathway and the c-Jun N-terminal kinase (JNK) signaling pathway. Specifically, the compounds suppress the IIS pathway and activate the JNK pathway to promote DAF-16 nuclear translocation, thereby regulating the expression of downstream target genes and exerting anti-aging effects.