Almond ( Amygdalus communis L.) Peptides Improve Scopolamine‐Induced Learning and Memory Impairment in Mice

ABSTRACT In this study, almond peptides (APs) were prepared via efficient enzymatic hydrolysis with DH (55.22% ± 0.56%) and peptide yield (77.92% ± 0.92%), then 1315 peptides were identified using LC‐MS/MS and peptides (Mw < 3 kDa) amounted to 99.62%. Through molecular docking analysis, 90 peptides and 92 peptides in APs were respectively predicted to be AChE and Keap1 inhibitors. MWM behavioral test results showed that escape latency was reduced, crossing times in the target platform were increased, as well as loss of hippocampal neuronal was alleviated, indicating that APs could improve learning and memory in scopolamine‐induced mice. And APs ameliorated cholinergic dysfunction by elevating levels of ACH, AChR, and ChAT while inhibiting AChE activity. Meanwhile, APs mitigated oxidative stress by increasing antioxidative enzymes activities and lowering MDA level, and inflammatory responses were decreased through reducing NO, TNF‐α, and IL‐6 expression. Furthermore, APs regulated Nrf2/Keap1 signaling pathway by activating Nrf2 transcription factor and downregulating Keap1 protein to facilitate antioxidant defenses. Moreover, APs modulated metabolites such as gamma‐aminobutyric acid, 2‐phenylethanol, and six metabolic pathways, which are associated with improving memory. The results indicate that APs prepared by enzymatic hydrolysis may be helpful to alleviate the memory impairments.