Vitexin and Isovitexin Act through Inhibition of Insulin Receptor to Promote Longevity and Fitness in Caenorhabditis elegans

Scope Vitexin and isovitexin are natural plant nutraceuticals for human health and longevity. This research investigates the underlying mechanisms of vitexin and isovitexin on aging and health. The vital role of DAF-2/insulin-like growth factor-1 receptor (IGFR) is illustrated in the insulin/insulin-like growth signaling pathway (IIS) modulated by vitexin and isovitexin. Methods and results In vitro, in vivo models and molecular docking methods are performed to explore the antiaging mechanism of vitexin and isovitexin. Vitexin and isovitexin (50 and 100 mu M) extended the lifespan of Caenorhabditis elegans. The declines of pharyngeal pumping and body bending rates, and the increase of intestinal lipofuscin accumulation, three markers of aging, are postponed by these compounds. They inhibit IIS pathway in a daf-16-dependent manner, subsequently increasing the expressions of DAF-16 downstream protein and gene in nematodes. Molecular docking studies demonstrate that these compounds mightinhibit insulin signal by binding to the crucial amino acid residue ARG1003 in the pocket of IGFR. Western blot indicates that IGFR, PI3K, and AKT kinase expressions in senescent cells are decreased after vitexin and isovitexin treatment. Conclusion Vitexin and isovitexin may inhibit IIS pathway by occupying adenosine-triphosphate binding site pocket of IGFR, subsequently decreasing IGFR expression, thereby promoting longevity and fitness.