Oxidative stress causes damage to cells and brain injury-associated disorders. The study aimed to investigate how the tripeptide Phe-Pro-Phe (FPF), derived from an antioxidant-rich Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR), could protect against oxidative stress caused by scopolamine. Utilizing mouse and cell models to induce oxidative stress injury with scopolamine, coupled with Fourier transform infrared (FTIR) microscopy, immunofluorescence, and mitochondrial function assays, the study demonstrated that FPF significantly reduced malondialdehyde (MDA) and reactive oxygen species (ROS) levels, as well as decreasing the expression level of the apoptotic protein Caspase-3, while also increasing superoxide dismutase (SOD) activity and unsaturated lipid levels. Furthermore, FPF significantly improved mitochondrial aerobic respiration oxygen consumption rate (OCR) and anaerobic glycolytic metabolism extracellular acidification rate (ECAR) in mouse hippocampal neuron (HT22) cells. The results indicated that FPF protected against scopolamine-induced oxidative stress by regulating anti-oxidative activity, enhancing Caspase-3 expression, increasing unsaturated lipid levels, and improving cellular energy metabolism.
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