# Cyanidin-3-O-Glucoside Protects Against Cognitive Impairment in D-Galactose-Induced Aging Mice by Regulating Nrf2 and NF-κB Pathways

## TL;DR

Cyanidin-3-O-glucoside (C3G) helps protect against brain aging in mice by reducing oxidative stress and inflammation through specific molecular pathways.

## Contribution

This study reveals the molecular mechanisms by which C3G protects against cognitive decline in aging mice.

## Key findings

- C3G improved cognitive function and reduced hippocampal damage in aging mice.
- C3G enhanced antioxidant activity and reduced pro-inflammatory cytokines.
- C3G modulated Nrf2 and NF-κB pathways to reduce oxidative stress and inflammation.

## Abstract

Background/Objectives: This study aimed to investigate the protective effects and underlying molecular mechanisms of cyanidin-3-O-glucoside (C3G) against cognitive impairment in aging mice induced by D-galactose (D-gal). Methods: Spatial learning and memory, hippocampal histopathology, oxidative stress and inflammatory markers, as well as underlying regulatory pathways, were assessed in C3G-treated D-galactose-induced aging mice via Morris water maze, H&E staining, biochemical assays, qRT-PCR and Western blot. Results: Results showed C3G improved cognitive function by reducing escape latency and increasing target quadrant time along with platform crossings, while also alleviating hippocampal damage. It dose-dependently enhanced total antioxidant capacity and activities of key antioxidant enzymes (GSH-Px and SOD), reduced malondialdehyde, and inhibited pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). At the molecular level, C3G treatment was associated with changes in the Nrf2 and NF-κB pathways at mRNA and protein levels. It enhanced Nrf2 expression and reduced Keap1 expression, accompanied by upregulated mRNA levels of Nqo1 and Hmox1. Meanwhile, C3G decreased IKKβ and p65 protein expression and downregulated mRNA levels of Ikbkb, Nfkb1, and RelA. The combined contribution of these pathways in reducing ROS and inflammation may constitute the molecular basis underlying the neuroprotective effects of C3G. Conclusions: C3G alleviates cognitive dysfunction and brain damage in D-gal-induced aging mice, with effects associated with modulation of Nrf2 and NF-κB pathways. These findings offer preliminary insights for its dietary application in brain aging intervention.