Abstract:The mechanism of γ-[Glu](1≤n≤4)-Trp and its peptide monomers (γ-Glu-Trp, γ-[Glu]2-Trp, γ-[Glu]3-Trp, and γ-[Glu]4-Trp) on anxiety-like behavior and serotonin synthesis was investigated using a zebrafish model. The anxiety-like behaviors (increased time in the light area in light-dark test, number of up-and-down shuttles in novel tank test) were reduced two weeks after administration of 56 μg/mL γ-[Glu](1≤n≤4)-Trp and 500 μg/mL of each monomer. γ-Glu-Trp was most effective (41.66% of time in light, 25.83% up-and-down shuttles). γ-[Glu](1≤n≤4)-Trp and its peptide monomer induced up-regulation of tryptophan-serotonin (Trp-5-HT) metabolism by increasing Trp concentration and tryptophan hydroxylase activity in zebrafish. The in vivo findings demonstrate that γ-[Glu](1≤n≤4)-Trp and its peptide monomer have significant anti-anxiety effects as evidenced by reduced anxiety-like behavior, increased 5-HT level, and induced up-regulation of Trp-5-HT metabolism pathway in zebrafish treated with γ-[Glu](1≤n≤4)-Trp and its peptide monomer compared to that in the control group. These results suggest that dietary γ-[Glu](1≤n≤4)-Trp and its peptide monomer may induce beneficial effects for anxious behavior.
