Antidepressant-like effect of food-derived pyroglutamyl peptides in mice

Yamamoto, Yu; Maekawa, Takafumi; Mori, Yukiha; Shimmura, Yuki; Fukutomi, Ruuta; Kanamoto, Ryuhei; Ohinata, Kousaku

doi:10.1016/j.npep.2015.04.002

Cited by 34 publications

(24 citation statements)

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“…forced swim test. The forced swim test (FST) was performed as previously described 40 . The total immobility time of mice was assessed according to Porsolt et al 41 .…”

Section: Discussionmentioning

confidence: 99%

“…A decrease in the immobility time was set as an indicator of an antidepressant-like effect. Previous studies www.nature.com/scientificreports www.nature.com/scientificreports/ showed that dipeptide and tripeptide affected brain functions, producing depressive, anxiety, and cognitive effects 30 min after peptide administration 1,8,[38][39][40]42 . FST was started 30 min after administration of the peptide or saline orally, intracerebroventricularly, or intraperitoneally.…”

Section: Discussionmentioning

confidence: 99%

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Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Maekawa

Uchida

Ohinata

2020

Sci Rep

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Depression is a worldwide health problem. In the present study, we found that a dipeptide, tyrosyl leucine (Tyr-Leu, YL), administered orally, intracerebroventricularly, or intraperitoneally exhibited a potent antidepressant-like activity in the forced swim and tail suspension tests in naïve mice. YL increased the amount of cells expressing c-Fos, a marker for neuronal activity, in the dentate gyrus of the hippocampus. YL increased bromo-2′-deoxyuridine-positive cells and doublecortin expression in the dentate gyrus of the hippocampus, suggesting that YL enhanced the proliferation of hippocampal progenitor cells in vivo and in vitro. YL did not affect hippocampal mRNA and protein expression of BDNF, which is a regulatory factor of both neurogenesis and depression-like behavior. Intriguingly, YL suppressed activation of the hypothalamo-pituitary-adrenal axis by forced swim stress. Moreover, other aromatic amino acid-leucines, Phe-Leu and Trp-Leu, also exhibited antidepressant-like activities, suggesting that the structure of aromatic amino acid-leucine may be important for antidepressant activity. In addition, bovine milk casein-derived peptide, Tyr-Leu-Gly (YLG), an anxiolytic peptide, exhibited an antidepressant-like activity. Our findings demonstrate that YL exhibits an antidepressantlike effect, moderates the stress response, and induces hippocampal neuronal proliferation through a signal pathway independent of BDnf.A number of bioactive peptides have been found in enzymatic digests of various food proteins, and some of these peptides are known to act on the nervous system. We also reported that bioactive peptides derived from food proteins exhibit anxiolytic-like effects 1-7 , suggesting interactions between food components and the nervous system. Clarification of these interactions is challenging, since the food components, including food protein digests, consist of numerous molecular species. On the other hand, we have found novel bioactive peptides based on the structure-activity relationships of dipeptides. Thus, the discovery of dipeptides with potent activities and the their structure-activity relationships are very important and powerful clues to find novel peptides. Indeed, we initially found that a dipeptide, tyrosyl leucine (Tyr-Leu, YL), had a potent anxiolytic-like effect, comparable to that of diazepam, one of the general anxiolytics, in mice 1 . Thereafter, based on the structure rule required for the anxiolytic activity of YL, novel food-derived peptides have been rapidly been identified. Thus, we focused on dipeptides.Major depressive disorder, one of the most common psychiatric diseases, is characterized by dysregulation of emotion and mood as well as abnormalities of cognitive function, sleep, appetite, and metabolism. It is known to be a leading cause of disability worldwide 8,9 . Anxiolytic molecules often exhibit antidepressant-like effects. Thus, in the current study, we investigated whether YL exhibits antidepressant-like activities using two behavioral tests commonly used to screen ant...

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“…forced swim test. The forced swim test (FST) was performed as previously described 40 . The total immobility time of mice was assessed according to Porsolt et al 41 .…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Maekawa

Uchida

Ohinata

2020

Sci Rep

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“…We used male Deutschland, Denken, and Yoken (ddY) mice (SLC, Shizuoka, Japan) for behavioral tests and immunohistochemistry. This ddY strain is a closed colony with a rapid growth rate and high reproductive potential and has frequently been used in biomedical research, including behavioral pharmacological tests (9)(10)(11)(12)(13)(14)(15). Five-week-old mice (24228 g) were used for behavioral tests and immunohistochemical experiments.…”

Section: Animalsmentioning

confidence: 99%

“…These food proteinderived peptides sometimes act on the nervous system and affect emotional behavior. Indeed, we previously found that many anxiolytic-like peptides derived from food proteins, including as-casein, b-lactoglobulin, ovalbumin, and b-conglycinin originating from bovine milk, eggs, and soybeans, respectively, exhibit anxiolytic-like effects even after oral administration (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). In this study, we focused on the antidepressant-like effects of foodderived peptides.…”

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confidence: 99%

Characterization of soy‐deprestatin, a novel orally active decapeptide that exerts antidepressant‐like effects via gut–brain communication

et al. 2018

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We found that the orally administered thermolysin digest of β-conglycinin exhibits antidepressant-like effects in tail suspension and forced swim tests in mice. A comprehensive peptide analysis of the digest using liquid chromatography/mass spectrometry was performed, and LSSTQAQQSY emerged as a candidate antidepressant-like peptide. Orally administered synthetic LSSTQAQQSY exhibited antidepressant-like effects at a dose of 0.3 mg/kg; therefore, we named the decapeptide soy-deprestatin. In contrast, intraperitoneally administered soy-deprestatin was ineffective. We then hypothesized that it acted on the gut, and its signal was transferred to the brain. Indeed, orally administered soy-deprestatin exhibited antidepressant-like activity in sham-treated, but not vagotomized, mice. Oral administration of soy-deprestatin also increased the c-Fos expression in the nucleus of the solitary tract, which receives inputs from the vagus nerve. These results suggested that the antidepressant-like effects were mediated by the vagus nerve. Thermolysin digest- and soy-deprestatin-induced antidepressant-like effects were also blocked by antagonists of serotonin 5-HT, dopamine D, or GABA receptors. We also clarified the order of receptor activation as 5-HT, D, and GABA, using selective agonists and antagonists. Taken together, soy-deprestatin may exhibit antidepressant-like effects after oral administration via a novel pathway mediated by 5-HT, followed by D and GABA systems. This is the first orally active peptide demonstrating antidepressant-like effects via gut-brain communication.-Mori, Y., Asakura, S., Yamamoto, A., Odagiri, S., Yamada, D., Sekiguchi, M., Wada, K., Sato, M., Kurabayashi, A., Suzuki, H., Kanamoto, R., Ohinata, K. Characterization of soy-deprestatin, a novel orally active decapeptide that exerts antidepressant-like effects via gut-brain communication.

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“…pGlupro may be formed upon heating of the barley sprouts during malting or wort boiling. Pyroglutamyl peptides have been suggested to act on inflammatory diseases 16,37,38 and have been shown to exhibit an antidepressant-like effect in mice 39 . To our knowledge, pGlu-Pro has not previously been observed in beer samples or associated with an increase in blood or urine after beer intake.…”

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confidence: 99%

Detecting Beer Intake by Unique Metabolite Patterns

et al. 2016

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Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

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Antidepressant-like effect of food-derived pyroglutamyl peptides in mice

Cited by 34 publications

References 36 publications

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Dipeptide tyrosyl-leucine exhibits antidepressant-like activity in mice

Characterization of soy‐deprestatin, a novel orally active decapeptide that exerts antidepressant‐like effects via gut–brain communication

Detecting Beer Intake by Unique Metabolite Patterns

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