Mikako Sato

Carnosine-induced antidepressant-like activity in rats

Depression is a pathological state of mood and is considered as one of the major causes of disabilities. Thus, the prevention of depression and care for individuals with depression is important. In the present study, we examined whether a single oral dose of CBEX (chicken breast extract), or carnosine (one of the major components of CBEX) affects immobility time, an index of depressive-like behavior, in the forced swimming test in male Wistar rats. CBEX tended to (P=0.09) and carnosine significantly (P<0.05) decreased immobility time in the forced swimming test. In the hippocampus, both CBEX and carnosine significantly decreased 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine, indicating that CBEX and carnosine could reduce NE activity in the hippocampus in the forced swimming test. CBEX and carnosine did not affect total locomotive distance or rearing in the open field test, suggesting that the reductions of immobility time by both treatments in the forced swimming test were not merely due to the stimulation of general motor activity. Taken together, these results suggest that CBEX has an antidepressant-like effect, which may be due, in part, to the effect of carnosine.

The Bioavailable Octapeptide Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro Stimulates Nitric Oxide Synthesis in Vascular Endothelial Cells

Gly-Ala-Hyp-Gly-Leu-Hyp-Gly-Pro (GAXGLXGP, X: Hyp), an octapeptide contained in chicken collagen hydrolysate, inhibits angiotensin I-converting enzyme activity in vitro. Intestinal Caco-2 and bovine aortic endothelial cells (BAECs) were used to investigate whether the transported GAXGLXGP improves vascular function. When GAXGLXGP was added to the apical side of Caco-2 monolayers, the intact form of GAXGLXGP was released to the basolateral side without incorporation into the cells. This transport was energy-independent but was associated with tight junction permeability. GAXGLXGP was then added to BAECs, and endothelial nitric oxide (NO) synthase (eNOS) activation was examined. GAXGLXGP at a concentration of 10 microM stimulated production of NO during a 1 h incubation. This event involved phosphorylation of eNOS at Ser(1179) without a change in the total eNOS protein level. These findings indicate that GAXGLXGP absorbed intact through the intestinal epithelium has direct effects on eNOS activity in vascular endothelial cells, leading to NO synthesis, thereby suggesting the potential for improvement in vascular function.

Oral administration of chicken breast extract increases brain carnosine and anserine concentrations in rats

Abstract Carnosine (β-alanyl-L-histidine) and its derivative anserine (β-alanyl-1-methyl-L-histidine) are antioxidants and putative neurotransmitters in the brain. These dipeptides are rich in the commercially available supplement chicken breast extract (CBEX). To clarify the effects of CBEX on the brain, we examined whether single oral administration of CBEX (20 ml/kg) affects brain dipeptide and free amino acid concentrations in male Wistar rats. CBEX significantly and time-dependently increased carnosine and anserine levels in the plasma (at 120 min after injection, increase rates were 2976 and 4142%, respectively), hippocampus (64 and 78%), and hypothalamus (188 and 120%), but not in cerebral cortex. Significant and time-dependent increases in citrulline in the hippocampus (49%) and hypothalamus (41%) demonstrated generation of nitric oxide due to the increased carnosine and/or anserine levels in these brain regions. These findings suggest that CBEX modifies brain functions by increasing levels of these dipeptides.

Molecular Size of Collagen Peptide Reverses the Permeability of Caco-2 Cells

Intestinal permeability to size-classified fish collagen peptides (FCPs) was examined using Caco-2 monolayers. Minimum-sized FCPs were most efficiently transported across the Caco-2 monolayers. Permeability depended on peptide size. It was independent of the H+-coupled peptide transport system but was associated with tight junction permeability, suggesting that the paracellular pathway is responsible for transepithelial transport of collagen peptides.

mRNA Expression of Lysyl Oxidase and Matrix Metalloproteinase-12 in Mouse Skin

Elastic fibers in the dermis play an important role in skin elasticity. The desmosine crosslinking structure constructed of lysyl oxidase (LOX) in elastic fibers contributes to elasticity, while elastic fibers are primarily degraded by one of the matrix metalloproteinases (MMPs), MMP-12. We investigated the gender differences and diurnal variation of these enzymes. Gender-based differences in LOX mRNA expression were detected, and were significantly lower in females. In contrast, higher MMP-12 mRNA expression was observed in the light period, suggesting that elastic fibers might be degraded in the light rather than the dark period.

Dietary animal proteins alter monoamine metabolism in the brain

Several amino acids have effects on mental function, including sedative, antidepressant-like and anxiolytic-like effects. However, the influence of integrated amino acid nutrition as protein constituents on mental function remains unclear. Therefore, the purpose of the present study was to compare the influence of chicken, pork and beef protein extracts on brain monoamine metabolism in mice. Changes in monoamine levels and their turnover rates in the brain were induced by different protein sources. In particular, chicken protein group showed the highest norepinephrine levels in the hippocampus and hypothalamus, and beef protein extract caused an activation of the serotonergic system in the hypothalamus, although there were no significant differences in amino acid compositions of these protein extracts. Therefore, it was revealed that amino acid compositions in dietary protein did not induce alteration in monoamine metabolism. However, there were differences in small molecular peptides, such as creatine, carnosine and anserine levels in animal protein extracts. In conclusion, monoamine metabolism was altered by dietary protein sources. However, it was indicated that the alteration in monoamine metabolism may be independent from amino acid compositions in dietary protein. In addition, alteration in monoamine metabolism depending on the dietary protein sources may be induced by small molecular peptides.

Expression profiles of carnosine synthesis–related genes in mice after ingestion of carnosine or β-alanine

BackgroundCarnosine is a dipeptide that improves exercise performance. The carnosine synthesis mechanism through carnosine and β-alanine ingestion remains unclear. Therefore, we investigated the tissue distribution of carnosine synthase, ATP-grasp domain-containing protein-1 (ATPGD1) mRNA, and ATPGD1 and carnosine specific dipeptidase (CN1) gene expression profiles in mice that were given carnosine or β-alanine orally.MethodsddY mice (7-week-old) were randomly divided into three groups (n = 6 to 8 animals per group) and were orally given 2 g/kg body weight of carnosine, β-alanine, or water. After 15, 30, 60, 120, 180, or 360 min of treatment, the tissues (brain, blood, liver, kidneys, olfactory bulbs, hindleg muscles) were collected. The obtained tissues measured the expression of ATPGD1 and CN1 genes using quantitative PCR methods.ResultsThe ATPGD1 gene was expressed in muscle and to a lesser extent in brain. The expression of ATPGD1 in the vastus lateralis muscle increased significantly at 180 min (P = 0.023) after carnosine ingestion and 60 (P = 0.023) and 180 min (P = 0.025) after β-alanine ingestion. Moreover, the carnosine group showed a significantly increased renal expression of the CN1 gene 60 min after ingestion (P = 0.0015).ConclusionsThe ATPGD1 gene showed high expression levels in brain and muscle. The β-alanine or carnosine administration significantly increased ATPGD1 and CN1 expression in mice.

Vasoprotective Effect of Foods as Treatments: Chicken Collagen Hydrolysate

Collagen is a major protein in living organisms and accounts for about one-third of all protein in mammalian bodies, including the human body. Recently, collagen peptides have been used as foods that take advantage of their tertiary functions. We have been focusing on the vasoprotective effect of collagen peptides. Chicken collagen hydrolysate (CCH) is obtained by treating chicken feet with enzymes to produce an angiotensin-converting enzyme (ACE) inhibitory peptide. Administration of this CCH for 12 weeks reduces blood pressure in humans. We therefore investigated the mechanism of the vasoprotective effect of CCH. We tested whether prolonged CCH treatment of rats or mice would restore endothelial cell function and improve proinflammatory cytokine levels. We found that CCH treatment improved the vasorelaxation of rat aorta damaged with L-NG-nitroarginine methyl ester , an NO synthesis inhibitor. CCH treatment also reduced the serum levels of IL-6, sICAM-1, and TNF-α in an atherosclerotic mouse model, C57BL/6.KOR-ApoEsh1. These findings indicate the usefulness of collagen peptides as foods promoting antiatherogenesis via a vasoprotective effect. Years have passed since functional foods and their tertiary function first attracted attention. The primary function of foods is to supply the nutrients required to sustain life, and the secondary function is to satisfy taste preferences. The tertiary function of foods is to exert biological regulatory effects, such as biophylaxis, homeostatic maintenance, and disease prevention, which are activated upon food intake. Purified food ingredients that have tertiary functions are widely consumed as supplements. Multitudes of supplements are available on today’s market: besides common vitamins, minerals, and amino acids, there are catechins, which are antioxidant constituents of tea (Katiyar, 2003), soy isoflavones, which have female hormone–like actions (Weijer, 2002), and docosahexaenoic acids and eicosapentaenoic acids, which decrease triglyceride levels (Tamai, 2004). Collagen is being used widely, not only in supplements but also as an ingredient of common food products such as beverages, yogurts, and breads. Collagen is a major protein in living organisms and accounts for about one-third of all protein in mammalian bodies, including the human body. It forms an extracellular matrix that plays a role in the formation of connective tissues and acts as a scaffold for cells, but its accumulation declines with age. The majority of the collagen in the body exhibits a triple

Mechanisms of carnosine-induced activation of neuronal cells

Abstract Carnosine (β-Ala-l-His), an imidazole dipeptide, is known to have many functions. Recently, we demonstrated in a double-blind randomized controlled trial that carnosine is capable of preserving cognitive function in elderly people. In the current study, we assessed the ability of carnosine to activate the brain, and we tried to clarify the molecular mechanisms behind this activation. Our results demonstrate that carnosine permeates the blood brain barrier and activates glial cells within the brain, causing them to secrete neurotrophins, including BDNF and NGF. These results point to a novel mechanism of carnosine-induced neuronal activation. Our results suggest that carnosine should be recognized as a functional food factor that helps achieve anti-brain aging. Graphical abstract Schematic diagram of carnosine function in the brain.

Impacts of acute imipramine treatment on plasma and brain amino acid metabolism in mice given graded levels of dietary chicken protein.

Several studies have shown a relationship between depression and animal protein intake. To evaluate whether the difference of dietary chicken protein levels induces an antidepressant-like effect and potentiates acute antidepressant effects, three levels of dietary chicken protein were used as the representative animal protein with imipramine used as the antidepressant. In addition, the effects of dietary chicken protein on brain metabolism were evaluated. Open field test (OFT) and forced swimming test (FST) were conducted on the 27th and 28th days, respectively. OFT and FST were not influenced by both imipramine and dietary protein levels. However, characteristic effects of imipramine treatment on brain monoamine metabolism were observed in the cerebral cortex and hypothalamus. In addition, dietary protein significantly increased taurine and L-ornithine levels even though these amino acids were not contained in the diets. In conclusion, the metabolism of several amino acids in the plasma and brain were altered by dietary chicken protein.