Inhibiting NF-κB activation and ROS production are involved in the mechanism of silibinin's protection against D-galactose-induced senescence.

Aging is featured by intelligence decline, behavioral disorders and cognitive disability. Autophagy is related to senescent development. In this study, we investigated the roles of NF-κB and autophagy in hippocampal neurons of D-galactose-induced senescent mice, and examined the protective roles of silibinin. Senescence was induced in 6-month-old mice by subcutaneous injection of D-galactose (150 mg/kg/d, for 6 weeks). Silibinin (50 mg/kg/d, intramuscular injection, for 6 weeks) or inhibitors (PDTC, 3-MA or rapamycin, 50 mg/kg/d, subcutaneous injection, for 6 weeks) were given 1 h before D-galactose exposure. Senescent control animals received vehicle for the same time. Ethological analysis, immunofluorescence staining, flow cytometric analysis, western blot and enzyme activity assays were used. Compared with senescent controls, silibinin, PDTC or rapamycin-treated mice showed upregulations of spatial recognition memory (P<0.05), cellular oxidoreductase activities (P<0.05) and autophagy (P<0.05) as well as downregulations of MDA (P<0.05) and ROS (P<0.05) levels. We propose in D-galactose-induced murine senescence, autophagy is inhibited by NF-κB, inducing the deactivations of cellular oxidoreductases and upregulation of ROS level. The protection by autophagy and the promotion of cellular oxidoreductase activities via inhibiting NF-κB activation and ROS production are involved in the mechanism of silibinin's protection against D-galactose-induced senescence.