Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins

Astragalin (AG), a typical flavonoid found inThesium chinenseTurcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG inCaenorhabditis elegans(C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. InC. elegans, AG synergistically extended the lifespan ofC. elegansby up-regulating the expression ofdaf-16through inhibiting the expression ofdaf-2/IGFRand also activating the AMPK and MAPK pathways to up-regulate the expression ofsir-2.1,sir-2.4, andskn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels ofSIRT1andSIRT6within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression ofIGFRthrough high levels ofSIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.