2. Academic Validation
  3. Walnut-derived peptides ameliorate d-galactose-induced memory impairments in a mouse model via inhibition of MMP-9-mediated blood-brain barrier disruption

Walnut-derived peptides ameliorate d-galactose-induced memory impairments in a mouse model via inhibition of MMP-9-mediated blood-brain barrier disruption

  • Food Res Int. 2022 Dec;162(Pt A):112029. doi: 10.1016/j.foodres.2022.112029.
Qiao Dang 1,  Dan Wu 1,  Yanru Li 1,  Li Fang 1,  Chunlei Liu 1,  Xiyan Wang 1,  Xiaoting Liu 1,  Weihong Min 2
Affiliations

Affiliations

  • 1 College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, PR China; National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, PR China.
  • 2 College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, PR China; National Engineering Laboratory of Wheat and Corn Deep Processing, Changchun 130118, PR China. Electronic address: [email protected].
PMID: 36461249 DOI: 10.1016/j.foodres.2022.112029
Abstract

Disruption of the blood-brain barrier (BBB) has been observed in several neurological diseases. This study explored the protective effect of the walnut-derived peptide TWLPLPR (TW-7) against d-galactose (d-gal)-induced cognitive disturbance in mice and its potential protection mechanism in β-amyloid 25-35 (Aβ25-35)-injured bEnd.3 cells. TW-7 improved the learning ability and memory of the cognitive impairment mice. Transmission electron microscopy showed that the BBB integrity in the hippocampus was restored; while immunofluorescence analysis and western blotting indicated that the protection of BBB integrity was associated with increased expression levels of tight junction (TJ) proteins. In Aβ25-35-damaged bEnd.3 cells, treatment with a matrix metalloproteinase 9 (MMP-9) activator and inhibitor confirmed that TW-7 partially reduced MMP-9 expression and increased zonula occludin-1 (ZO-1) and Claudin-5 expression. Furthermore, TW-7 reduced MMP-9 levels by forming stable complexes with it and by inhibiting the NF-κB p65/iNOS pathway. These data suggested that TW-7 maintains BBB integrity by inhibiting the expression and activity of MMP-9, and TW-7 improves learning and memory ability in mice.

Keywords

Blood-brain barrier; Cognitive impairment; MMP-9; Tight junction; Walnut-derived peptides; d-galactose.

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