Hydrolyzed Chicken Meat Extract Attenuates Neuroinflammation and Cognitive Impairment in Middle-Aged Mouse by Regulating M1/M2 Microglial Polarization

Aging is the most common cause of several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The pathological hallmarks of age-dependent neuropathology consist of chronic neuroinflammation, oxidative stress, gliosis, learning disability, and cognitive decline. A novel hydrolyzed bioactive peptide mixture extracted from chicken meat, that is, hydrolyzed chicken extract (HCE) has been previously demonstrated to exert neuroprotective effects in rodents and humans. However, the mechanism of HCE on age-related neurological disorders remains unclear. Herein, we aimed to clarify the impact and mechanism of isolated bioactive components (BCs) from HCE on age-dependent neuroinflammation and cognitive impairment in middle-aged mice. We found that both BC and HCE supplementation ameliorated age-induced memory loss, alleviated hippocampal neuroinflammation and oxidative stress, followed by promoting hippocampal neurogenesis in mice. BC and HCE treatment also ameliorated age-dependent morphological anomalies and alleviated microgliosis and astrogliosis. In parallel, BC and HCE treatment showed a significant decrease in the NF-κB p65 and p38 MAPK signaling, which were associated with the enhancement of antioxidative enzymes activities. Furthermore, BC treatment attenuated the neuroinflammatory phenotypes by the decrease in M1-polarized microglia and the increase in M2-polarized microglia in vivo and in vitro. In addition, we found that cyclo(Phe-Phe), one of the cyclopeptides purified from BC, showed notable anti-inflammatory effects in BV2 cells. Taken together, BC might be used as a dietary supplement for alleviating age-dependent neuropathology in middle-aged individuals.