The protective effect and mechanism of mangiferin on D-galactose-induced oxidative stress and cognitive impairment in aging mice by an integrated network pharmacology and experimental validation strategy

Mangiferin (MAN) was a natural bioactive xanthone with remarkable antioxidative, anti-inflammatory, and antiapoptotic effects. The purpose of this study to determine the protective influence of MAN on D-galactose (D-gal)-induced aging and cognitive impairment, together with its underlying molecular mechanism. The network pharmacology molecular docking analysis revealed that MAN has a potential binding with aging-related oxidative stress and apoptosis proteins. In D-gal-induced aging mice, MAN could significantly reduce D-gal-induced histopathological changes of liver and brain tissues. Moreover, MAN administration obviously increased activities of antioxidant enzymes (SOD, T-AOC, GSH-Px, and CAT) and decreased levels of AChE and MDA in the serum, liver, or brain tissues. Additionally, MAN alleviated learning and memory disorders and improved the exploration ability. Western blotting and immunohistochemical analysis results revealed that MAN could regulate the expressions of PI3K/Akt/Nrf2 signaling pathway-related proteins and apoptotic-related proteins (Bax, Bcl-2, and Caspase-9) in the liver tissues. Therefore, these findings suggested that MAN can be used as a potent dietary supplement in functional foods for the protection against aging-related impairments. Mangiferin (MAN) was a natural bioactive xanthone with remarkable antioxidative, anti-inflammatory, and antiapoptotic effects. The purpose of this study is to determine the protective influence of MAN on D-galactose (D-gal)-induced aging and cognitive impairment, together with its underlying molecular mechanism.image