Epigenetic mechanisms that dysregulate gene expressions
may play
a significant role in the development of neurological disorders. However,
whether peptides can modulate epigenetic mechanisms remains elusive.
This work aimed to investigate the impact of pretreatment with walnut-derived
peptidesWHP and YVLLPSPKon DNA methylation in a low-grade
neuroinflammation model. The enriched KEGG pathways included oxidative
phosphorylation, riboflavin metabolism, ribosome, and pyrimidine metabolism,
which are associated with methylation modification by oral administration
of YVLLPSPK in mice with scopolamine-induced cognitive deficits. Furthermore,
when THP-1 cells (human acute monocytic leukemia cell line) were exposed
to lipopolysaccharide (LPS)-induced inflammation responses, both WHP
and YVLLPSPK markedly inhibited the level of Il-6 to 2.05 ± 0.76
and 1.29 ± 0.19 (p < 0.05) and also declined
the mRNA expression of Mcp-1 to 1.64 ± 0.02 and 3.29 ± 1.21
(p < 0.01), respectively. Meanwhile, YVLLPSPK
decreased the activities of DNA methyltransferases (DNMTs) to 1.03
± 0.02 and 1.20 ± 0.31 (p < 0.05) based
on Dnmt3b and Tet2, respectively. The results indicated that YVLLPSPK
modulated DNA methylation in embryonic and neural precursor cells
in creating new methylation patterns. Further trials are needed to
assess the mechanisms underlying DNA methylation changes through peptides
in the pathophysiology of neurological disorders.