Phillyrin Ameliorates Oxidative Stress in D-Galactose-Induced Senescence in the Brain of Mice by Regulating the Nrf2/ HO-1 Signaling Pathway

Abstract

Objective To investigate the effects of phillyrin on D-galactose (D-gal)-induced aging in the brain of mice and mechanism. Methods Institute of Cancer Research mice were intraperitoneally injected with D-gal 150 mg/kg to induce the aging model, and the mice were treated with phillyrin 5, 15, and 45 mg/kg once a day for 8 weeks. Results The memory impairment induced by D-gal in brain aging was ameliorated by phillyrin treatment, and the oxidative stress in the aging brain and serum was inhibited, as evidenced by increased superoxide dismutase, glutathione peroxidase enzyme activities, and decreased malondialdehyde levels. Additionally, the hippocampus damage has also been well improved by phillyrin. Moreover, the protein expressions of nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were markedly up-regulated and the expression of Keap-1 was down-regulated in the phillyrin group than that in the aging model group. Conclusion These findings suggest that phillyrin is effective in the prevention of age-related memory impairment, and the attenuation oxidative stress by activating the Nrf2/HO-1 signaling pathway in the hippocampus may be one of the mechanisms.