Active Peptide KF-8 from Rice Bran Attenuates Oxidative Stress in a Mouse Model of Aging Induced by d-Galactose

This study investigated the effects of a physiologically active peptide derived from rice bran (KF-8) on oxidative stress in d-galactose (d-gal)-induced aging mice and the underlying molecular mechanisms. The aging model was developed by subcutaneously injecting Institute of Cancer Research mice with 250 mg/kg d-gal daily for 12 weeks and simultaneously treating them with 30 mg/kg KF-8. The relative expression levels of Nrf2 and NF-κB in the liver were determined by the western blot. The regulation of Nrf2 and NF-κBp65 by KF-8 was further validated in NIH/3T3 cells. Compared with the control mice, the aging mice had significantly decreased body weights as well as superoxide dismutase and GSH-Px levels (p < 0.05); however, they had increased serum reactive oxygen species and malondialdehyde and 8-hydroxydeoxyguanosine levels accompanied by aortic and brain injuries. They also had elevated RAGE, TLR4, IκB, Bax, and caspase-8 expressions and NF-κB/p65 phosphorylation but reduced BcL-2 expression in the liver. Moreover, in vitro experiments demonstrated that the pretreatment of H₂O₂-treated NIH/3T3 cells with KF-8 significantly mitigated the NF-κB signaling and attenuated the Nrf2 nuclear transport (both p < 0.05). In conclusion, KF-8 treatment inhibited aging-induced oxidative stress-related organ injury in mice by attenuating NF-κB/p38 signaling and preserving Nrf2 activity.