Oxidative stress relief to longevity: mulberry-derived anthocyanins enhanced antioxidant defense via Nrf2/SKN-1 activation

Anthocyanin has been demonstrated that potential health-promoting and anti-aging through antioxidant activities, although the underlying mechanisms remain unclear. In this study, we identified cyanin-3-O-glucoside (61.7%) and cyanin-3-O-rutinoside (25.1%) as the primary components of mulberry fruit anthocyanin extracts (MFAE) using LC-MS/MS. Two experimental models including a hydrogen peroxide-induced hepatocyte oxidative damage and an age-synchronized Caenorhabditis elegans were established. These models were co-cultured with MFAE for varying time periods followed by comprehensive analyses of subcellular structures and comparisons of oxidative stress and senescence-related parameters across treatment groups. The expression levels of Nrf2/SKN-1 pathway-related genes and proteins predicted by molecular docking were investigated. The results demonstrate that MFAE treatment significantly alleviated H2O2-induced cellular oxidative damage, extended lifespan in C. elegans, and improved multiple health indices. Furthermore, MFAE activated the evolutionarily conserved Nrf2/SKN-1 pathway while modulating the expression of various upstream and downstream genes (gst-4, gcs-1, sod-3) and proteins (HO-1, P62, Keap1, BAX). These findings indicate that MFAE exerts anti-aging effects via antioxidant-driven activation of the Nrf2/SKN-1 pathway.