Fish scale collagen peptide improves neurodegenerative disorders by dual regulation of acetylcholinesterase activity and antioxidant defense system

BACKGROUND Memory impairment, a hallmark manifestation of neurodegenerative disorders exemplified by Alzheimer's disease, constitutes a critical global public health challenge requiring urgent therapeutic innovation. The present study aims to systematically investigate the potential mechanisms of fish scale collagen peptides (FSCP) in enhancing cognitive function through behavioral experiments, detection of hippocampal biochemical indicators and histopathological observation. Concurrently, liquid chromatography-tandem mass spectrometry analysis and in silico methods were utilized to screen active peptide fragments with potential auxiliary effects on memory improvement. RESULTS The results of our study demonstrated that mice treated with a medium dose of FSCP via gavage exhibited optimal behavioral performance. Moreover, the number of Nissl bodies in the CA1 and CA3 regions increased to (114.83 ± 8.74) and (71.67 ± 5.79), respectively. Hippocampal pathology was improved, Acetylcholine levels were elevated, Acetylcholinesterase ctivity was decreased and hippocampal oxidative stress was reduced in the mice. Among the digested products of FSCP, the tripeptides PPP, GGL, GLL and MAP were found to exhibit higher relative abundance and activity scores. CONCLUSION These results demonstrate that mice treated with a medium dose of FSCP via gavage exhibited the most substantial improvement in memory function. Bioactive peptides such as PPP and GGL are promising to provide a new source for the development of drugs for assisted memory improvement. © 2025 Society of Chemical Industry.