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    Vitexin and isovitexin are natural plant nutraceuticals for human health and longevity. This research investigated the underlying mechanism of vitexin and isovitexin on aging and health. The vital role of DAF-2/IGFR was illustrated in the insulin/insulin-like growth signaling pathway (IIS) modulated by vitexin and isovitexin.In vitro, in vivo models and molecular docking methods were performed to explore the antiaging mechanism of vitexin and isovitexin. Vitexin and isovitexin (50 and 100 μM) extended the lifespan of C. elegans. The declines of pharyngeal pumping and body bending rates, and the increase of intestinal lipofuscin accumulation, three markers of aging, were postponed by vitexin and isovitexin. These compounds inhibited the IIS pathway in a daf-16-dependent manner, subsequently increasing the expression of DAF-16 downstream proteins and genes in nematodes. Molecular docking studies demonstrated that these compounds might inhibit insulin signal transduction by binding to the crucial amino acid residue ARG1003 in the pocket of the insulin-like growth factor-1 receptor (IGFR). Western blot indicated that IGFR, PI3K and AKT kinase expressions in senescent cells is decreased after vitexin and isovitexin treatment.Vitexin and isovitexin might inhibit IIS pathway by occupying the ATP-binding site pocket of IGFR, subsequently decreasing IGFR expression, thereby promoting longevity and fitness. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

    Citation

    Mingfang Tao, Rong Li, Zhuo Zhang, Ting Wu, Tingting Xu, Daniel Zogona, Yuting Huang, Siyi Pan, Xiaoyun Xu. Vitexin and Isovitexin Act Through Inhibition of Insulin Receptor to Promote Longevity and Fitness in Caenorhabditis elegans. Molecular nutrition & food research. 2022 Apr 12:e2100845


    PMID: 35413150

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