Red cabbage anthocyanins may provide health benefits that may be associated with antiaging. The protection of red cabbage anthocyanin-rich extract (ARE) and cyanidin-3-diglucoside-5-glucoside-rich extract (CY3D5G) against age-related cognitive dysfunction was investigated in normal aging mice (male C57BL/6J, 12 months old) administered orally for 12 weeks. Behavioral tests showed that ARE and CY3D5G significantly decreased cognitive impairment (p < 0.05) and had no effect on motor disorder. ARE and CY3D5G increased superoxide dismutase activity by 29.18 and 23.09% and decreased malondialdehyde by 15.74 and 10.05%, respectively, compared to the control. Histological staining showed that ARE and CY3D5G treatment reduced hippocampal neuronal damage and brain-derived neurotrophic factor degeneration. ARE and CY3D5G significantly reduced IL-1β and IL-6 levels in serum and brain (p < 0.05) by promoting the MAPK signaling pathway while enriching the abundance of butyrate-producing bacteria and altering the functional profile of the microbial community. In conclusion, ARE and CY3D5G may attenuate age-related cognitive dysfunction by reducing neuroinflammation and regulating the gut–brain axis.
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