コウサンカ ショクヒン ノ ケンコウ ゾウシン コウカ ノ カガクテキ コンキョ : コウサンカ キノウ ワ カラダ オ ヨクスルカ

In Japan, the law “Food for Specified Health Uses : FoSHU” was started in 1991 as a result of advanced research on functional foods. Recently, research and development of functional foods has been a worldwide trend in food industry. Antioxidant activity is believed to be one of the important functions to estimate the physiological role of functional foods. Antioxidant foods containing a lot of antioxidant components, that is, vitamin E, vitamin C, carotenoids, flavonoids and so on, seems to be effective to promote human health because antioxidants can protect the body from severe oxidative stress leading to a variety of diseases. However, the scientific evidence has not been enough yet to explain the health promotion and disease prevention by the usage of antioxidant foods. Human studies, in particular, well-organized intervention studies, should be required to break through this situation

メンタル ヘルス オ ササエル エイヨウ カガク : ショクヒン セイブン ノ コウウツヨウ カッセイ ヒョウカ

Nowadays anti-stress effect of food ingredients attracts much attention from the standpoint of maintenance of mental health. Nevertheless, definitive evidence on the effect is very few in human studies. The University of Tokushima proceeded the２１st -Century COE Program,“Human Nutrition Science on Stress Control”, from ２００４ to ２００８. In this program, we carried out the screening and evaluation of antidepressant-like effect of plant polyphenols. It is suggested that plant polyphenols are able to suppress brain mitochondrial monoamine oixidase-A（MAO-A）activity which is responsible for the serotonin metabolism in synapses. In addition, intake of quercetin, a representative plant polyphenol, seems to affect hypothalamus-pituitary gland-adrenal cortex axis（HPA axis）leading to the suppression of plasma cortisol. It is therefore likely that plant polyphenols act as anti-stress ingredients from foods to contribute metal health, although more studies including human trials are obviously required

サンカ ストレス ト ショクヒン コウサンカ ブッシツ

Daily foods contain a variety of minor components which possess antioxidative activity, such as vitamin E and vitamin C. On the other hand, it has been well known that reactive oxygen species (ROS) generating in the body cause oxidative damages in the tissues and fluids, resulting in the generation and progress of life style-related diseases. Therefore, it should be expected that dietary antioxidants are well introduced to individual food-style from the viewpoint of disease prevention and health promotion. However, there are two important subjects to be clarified, that is, the mechanism by which they exert the antioxidant activity in vivo, and the site at which they act as antioxidants in vivo. We are interested in common components present in foodstuffs, in particular, carotenoids, flavonoids and phytic acid, and are challenging to solve these subjects by use of carotenoids and flavonoids. Here we will discuss the result of our recent studies on dietary flavonoids. We have claimed that flavonoids are interfacial antioxidants whose activities appear at the interface between lipid-phase and water-phase. Nevertheless, little is known on the absorption and metabolism of flavonoids from diet. We recently investigated the absorption and metabolic pathway of quercetin, a representative flavonoid in plant foods, using rats, humans and cultured cell derived from human digestive tract. The result shows that a part of quercetin is absorbed from digestive tract and exclusively accumulates as conjugated metabolites in blood plasma. The antioxidative activity of quercetin exhibited in blood plasma is likely to be originated from conjugated metabolites. It is therefore implied that metabolic products largely contribute to the physiological function of flavonoids, when flavonoids are ingested from daily foods

Dietary flavonoids as antioxidants in vivo : Conjugated metabolites of (-) -epicatechin and quercetin participate in antioxidative defense in blood plasma

Flavonoids are present in mainly plant foods and have attracted much atten-tion in relation to disease prevention. Their antioxidant activity at least partly accounts for their potential health effect, because oxidative stress leads to a variety of patho-physiological events. It is essential to know the bioavailability of flavonoids involving intestinal absorption, metabolic conversion and urinary excretion, in order to evaluate their in vivo antioxidant activity after intake. Here (-)-epicatechin and quercetin were selected as typical flavanol- and flavonol-flavonoids present in vegetables, fruits and tea. Our rat study suggests that their metabolic conversion begins in the intestinal mucosa where the activity of uridine-5'-diphosphoglucuronosyltransferase (UGT) is at its highest. Both flavonoids accumulated mostly as glucuronide and sulfate conjugates in blood plasma after oral administration. No intact quercetin was found in the circulation. However, on the oral administration of these flavonoids, the antioxidative ability of rat plasma was enhanced indicating that conjugated metabolites participate in the anti-oxidant defense in blood plasma. Therefore, the intake of vegetables, fruits and tea rich in flavonoids may help to prevent oxidative damages in the blood

ATP/P2X7R signaling as a target of natural polyphenols

Innate immune cells, such as macrophages, respond to pathogen-associated molecular patterns, such as a lipopolysaccharide (LPS), to secrete various inflammatory mediators. Recent studies have suggested that damage-associated molecular patterns (DAMPs), released extracellularly from damaged or immune cells, also play a role in the activation of inflammatory responses. In this study, to prevent excess inflammation, we focused on DAMPs-mediated signaling that promotes LPS-stimulated inflammatory responses, especially adenosine 5’-triphosphate (ATP)-triggered signaling through the ionotropic purinergic receptor 7 (P2X7R), as a potential new anti-inflammatory target of natural polyphenols. We focused on the phenomenon that ATP accelerates the production of inflammatory mediators, such as nitric oxide, in LPS-stimulated J774.1 mouse macrophages. Using an siRNA-mediated knockdown and specific antagonist, it was found that the ATP-induced enhanced inflammatory responses were mediated through P2X7R. We then screened 42 polyphenols for inhibiting the ATP/P2X7R-induced calcium influx, and found that several polyphenols exhibited significant inhibitory effects. Especially, a flavonoid baicalein significantly inhibited ATP-induced inflammation, including interleukin-1β secretion, through inhibition of the ATP/P2X7R signaling. These findings suggest that ATP/P2X7R signaling plays an important role in excess inflammatory responses and could be a potential anti-inflammatory target of natural polyphenolic compounds

血管内皮細胞における過酸化水素誘導のカベオリン-1リン酸化に対するケルセチンの抑制効果

Caveolin-1 is a major protein of the caveolae structure in vascular endothelial cell membrane. Phosphorylation of caveolin-1 is one of the initial events leading to exacerbation of vascular permeability caused by oxidative stress. Although quercetin is known to be an anti-atherosclerosis factor that acts as a dietary antioxidant, little is known about its role in the regulation of caveolin-1 phosphorylation. In this study, we investigated the inhibitory effect of quercetin on hydrogen peroxide-induced caveolin-1 phosphorylation in human umbilical vein endothelial cells. Quercetin inhibited caveolin-1 phosphorylation in cells pretreated with quercetin for 24 h and then exposed to hydrogen peroxide. However, quercetin 3-O-β-glucuronide, a conjugated metabolite of quercetin, did not exert this inhibitory effect. Exposure to hydrogen peroxide increased vascular permeability and reduced mRNA expression of the intercellular adhesion protein, vascular endothelial cadherin (VE-cadherin). By contrast, pretreatment with quercetin suppressed the increase in vascular permeability and decreased VE-cadherin expression. These results indicate that deconjugated quercetin can play a role in the prevention of altered vascular permeability under oxidative stress by suppressing caveolin-1 phosphorylation. Thus, dietary quercetin may be beneficial for the maintenance of endothelial cell function

Chocolate as a food matrix reduces the bioavailability of galloylated catechins from green tea in healthy women

In this study, we evaluated the food matrix effects of chocolate on absorption of green tea catechins (GTCs), (−)-epicatechin (EC), (−)-epigallocatechin (EGC), (−)-epicatechin gallate (ECg), and (−)-epigallocatechin gallate (EGCg), in five healthy 22-year-old women. In the single-intake experiment, the plasma concentrations of ECg (P < 0.05, at 1.5 h) and EGCg (P < 0.05, at 6 h) but not those of EC and EGC were reduced by the chocolate matrix. Regardless of the chocolate matrix, ECg and EGCg were mainly present as their aglycones in the plasma, whereas EGC and EC were found mostly as conjugated metabolites. After daily intake of GTCs mixed with chocolate for 14 days followed by overnight fasting, ECg but not EGCg was detected in the plasma. To compare the plasma profiles of ECg and EGCg, a mixture containing approximately equal amounts of ECg and EGCg was administered to nine rats for 14 days. Following treatment and overnight food deprivation, the plasma content of ECg was higher than that of EGCg. After a single injection of the same mixture in seven rats, ECg levels were higher than those of EGCg, and a greater amount of conjugated metabolites of ECg than those of EGCg was detected in the plasma 10 h after administration. In conclusion, the chocolate matrix affects the plasma profiles of GTCs, particularly ECg. ECg appears to persist in the plasma for a longer period, regardless of the chocolate matrix

Approach to novel functional foods for stress control : 5. Antioxidant activity profiles of antidepressant herbs and their active components

Oxidative stress is frequently mentioned in relation to the neurodegenerative diseases. This study examined the effect of three herb extracts, Hypericum perforatum, Ginkgo biloba L. and Apocynum venetum L., and their components on lipid hydroperoxide-induced oxidative stress in PC-12cells. Among them, the extract of Apocynum venetum and its components showed the remarkable inhibitory effect, indicating that this herb extract serves as a protective agent against lipid peroxidation-related oxidative stress in CNS. Oxidative stress may be associated with the progress of depression, as this extract has been proposed to be an effective antidepresant herb