Anti-aging effects of Ribes meyeri anthocyanins on neural stem cells and aging mice

Abstract

Aging is associated with neurological impairment and cognitive decline. Flavonoids are very promising in anti-aging research in mouse models. <i>Ribes meyeri</i> anthocyanins are rich in abundant flavonoids, but their anti-aging biological activities remain unknown. In this study, we prepared an <i>R. meyeri</i> anthocyanin extract and analyzed its effects on neural stem cell (NSC) senescence <i>in vivo</i> and <i>in vitro</i>. We isolated mouse NSCs and used cell counting kit-8 (CCK-8), cell cycle, reactive oxygen species (ROS), and immunofluorescence methods to analyze the anti-aging effects of <i>R. meyeri</i> anthocyanins as well as naringenin (Nar), which metabolic analysis revealed as an important flavonoid in <i>R. meyeri</i> anthocyanins. RNA-sequencing (RNA-seq) and enzyme-linked immuno sorbent assay (ELISA) methods were also used to investigate Nar-specific mechanisms of anti-aging. After <i>R. meyeri</i> anthocyanin treatment, NSC proliferation accelerated, and NSCs had decreased senescence markers, and reduced P16^ink4a expression. <i>R. meyeri</i> anthocyanin treatment also reversed age-dependent neuronal loss <i>in vivo</i> and <i>in vitro</i>. Nar blocked mNSC aging <i>in vitro</i> and improved spatial memory and cognitive abilities in aging mice through downregulation of plasma TNF-α protein. These findings suggest that <i>R. meyeri</i> anthocyanins increase NSC proliferation and improve neurogenesis with aging via Nar-induced reductions in TNF-α protein levels <i>in vivo</i>.