記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesame lignans, which are biologically active compounds present in sesame seeds and oil, are known to have neuroprotective effects in several models of brain dysfunction. However, the effects of sesame lignans on age-related brain dysfunction are not clear and were thus investigated in the present study using a senescence-accelerated mouse (SAMP10). Two-month-old male SAMP10 mice were administrated a basal diet with 0% or 0.05% sesame lignans for two months, or with 0%, 0.02%, or 0.05% sesame lignans for 10 months and subjected to step-through passive avoidance tasks and forced swim tests. Reactive carbonyl species (RCs) were evaluated as markers of oxidative stress using a recently developed comprehensive analytical method. Both learning time in passive avoidance tasks and immobile time in forced swim tests became longer with aging (p < 0.05). However, the administration of sesame lignans significantly ameliorated age-related effects in both tests (p < 0.05). Age-related increases in RCs such as 4-hydroxy-2-nonenal in the cerebral cortex and liver were reduced in mice fed sesame lignans. These results suggest that sesame lignans can prevent age-related brain dysfunction via anti-oxidative activity.

DOI： 10.3390/nu11071582

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse macrophage-like J774.1 cells and found that a monocatechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol-O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation.

DOI： 10.1021/acs.jafc.8b07227

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掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Sesamin is a major lignan constituent of sesame and possesses various health-promoting effects. Previous studies have demonstrated that sesamin extends the lifespan of Drosophila and Caenorhabditis elegans and corrects oxidative damage-related tissue dysfunction in mammals. To understand its anti-aging effects, we aimed to determine whether sesamin restores tissue function hampered by oxidative damage and suppresses several aging-related phenotypes using Drosophila senescence-accelerated models. MATERIALS AND METHODS: We elucidated the anti-aging effects of sesamin on several aging-related phenotypes in the muscle, brain and midgut using the senescence-accelerated models (Sod1 mutant and Sod1-depleted flies) by immunostaining experiments. We determined the expression levels of several anti-oxidative and DNA repair genes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We also identified the metabolite of sesamin in Drosophila by LC-MS/MS. RESULTS: We confirmed that sesamin (0.35 and 2 mg/ml) extended the lifespan of the fly models. As observed in mammals, it can be absorbed and metabolized by Drosophila adults. The sesamin feeding suppressed the age-dependent impairment of locomotor activity and inhibited the accumulation of reactive oxygen species (ROS) in their bodies. Sesamin delayed the age-dependent accumulation of damaged proteins in the muscle, partially suppressed the loss of dopaminergic neurons in adult brains displaying ROS accumulation, and suppressed the accumulation of DNA damage and hyperproliferation of intestinal stem cells. Four antioxidative genes and two DNA repair genes were simultaneously upregulated in sesamin-fed adults. CONCLUSIONS: These observations represent the first direct evidence of the anti-aging effects of sesamin at the individual level. We propose that sesamin exerts anti-aging effects in the muscles, brain and midgut by inducing antioxidative and DNA repair genes, resulting in extended lifespan in flies. n1

DOI： 10.26355/eurrev_201902_17146

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin is a major lignan in sesame seeds and oil. We previously demonstrated that sesamin induces chromosomal aberrations (CA) in Chinese hamster lung (CHL/IU) cells in the presence of a metabolic activation system (S9 mix), although no genotoxicity was detected in vivo. To clarify the mechanism of CA induction by sesamin, we identified its principal active metabolite. A mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (SC-1)], was previously identified in culture medium when sesamin was incubated with S9 mix. In the present study, we show that SC-1 induces CA in CHL/IU cells but not in human hepatoblastoma (HepG2) cells. SC-1 was unstable in culture medium. Addition of glutathione (GSH) to the incubation mixture decreased the rate of decomposition and also suppressed induction of CA in CHL/IU cells. These results indicate that SC-1 itself may not contribute to the induction of CA. Two GSH adducts of SC-1 were identified when SC-1 was incubated with GSH, suggesting that SC-1 was converted to the semiquinone/quinone form and then conjugated with GSH in the culture medium. Sodium sulfite (a quinone-responsive compound) also suppressed CA induction by SC-1. These findings strongly suggest that SC-1 is oxidized to semiquinone/quinone derivatives extracellularly in culture medium, that these derivatives are responsible for the induction of CA in CHL/IU cells, and therefore that the positive results obtained with sesamin in in vitro CA tests using CHL/IU cells may not be relevant to the assessment of in vivo activity.

DOI： 10.1016/j.mrgentox.2017.06.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

NEW FINDINGS: What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus. ABSTRACT: We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.

DOI： 10.1113/EP085251

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin has anti-oxidative functions in vivo. Fatigue is caused in part by oxidative stress. We evaluated whether sesame lignans (sesamin/episesamin=1/1, 10 mg) with vitamin E (55 mg of alpha-tocopherol) (SVE) could improve subjective statuses and anti-oxidative capacity in humans using questionnaires on fatigue, sleep and physical appearance, as well as low-density lipoprotein oxidation lag time. A placebo-controlled, double-blind, parallel-group study was conducted with subjects experiencing daily fatigue. After a run-in period, subjects were administered oral SVE or a placebo (P) for 8 weeks. A questionnaire regarding fatigue, sleep and physical appearance was conducted at 0, 4, and 8 weeks. Plasma low-density lipoprotein oxidation lag time was measured as an indicator of anti-oxidative capacity. The per-protocol analysis revealed significant improvements in fatigue status at 4 and 8 weeks compared to 0 weeks in both groups (p<0.01), and sleep and physical appearance at 8 weeks compared to 0 weeks only in the SVE group (p<0.01). There were no significant differences observed between the groups. According to the 72-subject subgroup analysis (aged 40 and over), the sleep and physical appearance significantly improved compared to the P group (p<0.05), and fatigue status showed a tendency for improvement compared to the P group. Anti-oxidative capacity in the SVE group significantly increased compared to the P group (p<0.01). No adverse events relating to SVE supplementation were confirmed. These results suggest SVE supplementation could safely alleviate daily fatigue and oxidative stress.

DOI： 10.5539/gjhs.v7n6p1

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掲載種別：研究論文（学術雑誌）  

Background and aim: The Mediterranean diet is reported to be effective in preventing cardiovascular disease (CVD). Olive polyphenols, grape seed oligomeric proanthocyanidins and vitamin C are major components of the Mediterranean diet. We evaluated combination effects of these compounds on vascular endothelial function as a surrogate marker for arteriosclerosis and CVD. Methods: A randomized, placebo-controlled, double-blind crossover trial was conducted. Seventy-two healthy subjects were randomly assigned to the test food group (50 mg of olive extract containing 6 mg of hydroxytyrosol, 100 mg of grape seed extract containing 60 mg of oligomeric proanthocyanidins and 100 mg of vitamin C) or the placebo group. The subject ingested each supplement for 4 weeks. After a washout period of 2 weeks, the other supplement was ingested for 4 weeks. Results: Flow-mediated vasodilation (FMD) was significantly improved by 4 weeks supplementation of the test food, and the change in FMD from baseline to 4 weeks was also significantly greater in the test food group than in the placebo group. Urinary 8-OHdG, an oxidative stress marker, and plasma high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, were significantly reduced in the test food group compared to the placebo group. No adverse events relating to test food supplementation were observed. Conclusions: These results suggest that the supplementation of olive and grape seed polyphenols with vitamin C could improve endothelial function via antioxidant and anti-inflammatory functions and that might be safe and effective for reducing the risk of arteriosclerosis and CVD.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. METHODS: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. RESULTS: In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren-Lawrence (K-L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, P<0.05) was significantly greater in the GCQID group than in the placebo group in subjects with K-L grade I. No adverse effect of treatment was identified in the safety assessment. CONCLUSION: In subjects with knee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions.

DOI： 10.2147/CIA.S93077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antioxidative effects of sesamin (a mixture of sesamin and episesamin) were evaluated in the liver, kidney and inferior vena cava of living rats using a radiofrequency ESR method. TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, was used as an in vivo redox probe, the half-life of which is believed to be correlated with the antioxidant status. The oral administration of sesamin (250 mg/kg rat weight) 3 h before ESR measurements shortened the half-life of TEMPOL in the liver by 10 - 15% as compared with the controls, but did not affect the other organs. This effect was maintained for at least 3 h after the administration, and then disappeared at 24 h, corresponding to the results of our preliminary pharmacokinetic studies. Changes in the reducing ability were observed only in the hepatic sites of the sesamin-treated rats. These findings suggest that sesamin exhibits effective antioxidant activity in the liver via modulation of the intracellular redox status related to TEMPOL reduction.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

DOI： 10.1017/S0007114512000141

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7'β,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-1-2) and (7α,7'β,8α,8'α)-3,4:3',4'-bis(dihydroxy)-7,9':7',9-diepoxylignane (EC-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1m-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-1m-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-2m-1) and (7α,7'β,8α,8'α)-3,4-dihydroxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their metabolites on Nrf2/ARE activation in rat pheochromocytoma PC12 cells. Luciferase reporter assays showed that primary metabolites of sesamin and episesamin, SC-1 and EC-1 were the most potent ARE activators among all tested compounds. SC-1 {(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane} enhanced nuclear translocation of Nrf2 and up-regulated expression of phase II antioxidant enzymes including heme oxygenase-1 (HO-1). Treatment with SC-1 resulted in increased phosphorylation of p38 MAP kinase and transient increase in intracellular ROS levels. N-acetylcysteine (NAC) treatment abolished p38 phosphorylation as well as HO-1 induction caused by SC-1, indicating that ROS are upstream signals of p38 in Nrf2/ARE activation by SC-1. Furthermore, preconditioning with SC-1 attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Finally, treatment with a HO-1 inhibitor, Zn-protoporphyrin (ZnPP), and overexpression of a dominant-negative mutant of Nrf2 diminished SC-1-mediated neuroprotection. Our results demonstrate that SC-1 is capable of protecting against oxidative stress-induced neuronal cell death in part through induction of HO-1 via Nrf2/ARE activation, suggesting its potential to reduce oxidative stress and ameliorate oxidative stress-related neurodegenerative diseases.

DOI： 10.1016/j.bmc.2011.01.059

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. To elucidate the molecular mechanism behind this effect, we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% α-tocopherol or sesamin + α-tocopherol for 10 days. Blood samples were collected on days 1, 3, 7, and 10 and livers were excised on day 10. The gene expressions of ATP-binding cassette, sub-family G (WHITE), members 5 (ABCG5) and 8 (ABCG8) were significantly increased, while the gene expression of apolipoprotein (Apo) A4 was significantly decreased. ABCG5 and ABCG8 form a functional heterodimer that acts as a cholesterol efflux transporter, which contributes to the excretion of cholesterol from the liver. ApoA4 controls the secretion of ApoB, which is a component of low-density-lipoprotein cholesterol. These studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin, a major lignan in sesame seeds, exhibits various health benefits. Here, we investigated effects of sesamin, its stereoisomer episesamin, and their metabolites on neuronal differentiation in rat pheochromocytoma PC12 cells. Among all compounds tested, primary metabolites of sesamin and episesamin, SC-1 and EC-1 {S- and R-epimer of 2-(3,4-methylenedioxyphenyl)-6-(3,4- dihydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane}, were the most potent to induce neuronal differentiation. SC-1 alone induced neuronal differentiation through extracellular signal-regulated kinase (ERK) 1/2 activation that is essential for nerve growth factor (NGF)-induced neuronal differentiation, as shown by the suppression with MEK1/2 inhibitors, PD98059 and U0126. However, SC-1 did not increase phosphorylation of TrkA, a high-affinity NGF receptor, and a TrkA inhibitor, K252a, did not affect SC-1-induced neuronal differentiation. Furthermore, SC-1 potentiated neuronal differentiation in cells co-treated with NGF, which was associated with enhanced ERK1/2 activation and increased expression of neuronal differentiation markers. Interestingly, when treated with SC-1 and a high dose of NGF, formation of synaptic connections and synaptophysin accumulation at the neurite terminals were markedly enhanced. These results indicate that (1) SC-1 alone induces neuronal differentiation, (2) SC-1 potentiates neuronal differentiation in NGF-treated cells, (3) SC-1 enhances formation of synaptic connections in cells treated with a high dose of NGF, all of which are associated with ERK1/2 activation. It is therefore concluded that SC-1 may promote neuronal differentiation by tapping into the ERK1/2-MAPK (mitogen-activated protein kinase) signaling pathway downstream from the TrkA receptor in PC12 cells. © 2009 Springer-Verlag.

DOI： 10.1007/s00702-009-0250-9

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掲載種別：研究論文（学術雑誌）  

Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical signincance with the administration of sesamin (systolic: 137.6±2.2 to 134.1±1.7 mmHg, p=0.044, diastolic: 87.7±1.3 to 85.8±1.0 mmHg, p=0.045), but little changed with the placebo (systolic: 135.0±1.8 to 135.1±1.7 mmHg, diastolic: 85.9±1.2 to 86.6±1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases.

DOI： 10.3177/jnsv.55.87

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have previously reported that substantial amounts of tocotrienols were present in the skin of animals fed a diet containing a tocopherols and tocotrienols rich fraction (T-mix) extracted from palm oil, and further, that sesame lignans enhanced tocotrienol levels in the skin. The present studies were undertaken to determine whether dietary tocotrienols and those with sesamin could protect the skin from damage induced by UVB irradiation in hairless mice fed four diets: a vitamin E-free diet, a 50 mg/kg alpha-tocopherol diet, a 229 mg/kg T-mix (with 50 mg alpha-tocopherol) diet and a 229 mg/kg T-mix with 2 g/kg sesamin diet. In Experiment 1, mice were fed the diets for 6 wk, and half of the mice were exposed to 180 mJ/cm(2 )of UVB light once daily for 7 d. After the intensity of sunburn was scored, vitamin E and thiobarbituric acid reactive substances (TBARS) concentrations in the skin and liver were determined. In Experiment 2, hairless mice were initiated with a single application of 7, 12-dimethylbenz[a]anthracene (DMBA), then 1 wk later mice were fed the experimental diets and subjected to 180 mJ/cm(2) UVB irradiation twice weekly for 20 wk. Tumor incidences were counted once a week. Tocotrienols were detected in the skin of mice fed T-mix, but their concentrations were significantly lower than for alpha-tocopherol. Sesamin elevated tocotrienol contents in the skin. In spite of the high alpha-tocopherol contents, the effects of alpha-tocopherol on sunburn and incidence of tumor were slight. T-mix fed groups reduced the extent of sunburn and incidence of tumor, and further reduction of sunburn and incidence of tumor were observed in the T-mix with sesamin group. These results suggest that dietary tocotrienols protect the skin more strongly than alpha-tocopherol against damage induced by UVB and sesamin enhances tocotrienol effects.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oolong tea-polymerized polyphenols (OTPP) are characterized polyphenols produced from semi-fermented tea (oolong tea). In the present study, we evaluated the suppressive effects of oolong tea extract and OTPP on postprandial hypertriglyceridemia in rats and mice. Lymphatic recovery of triglycerides in rats cannulated in the thoracic duct was delayed by the administration of oolong tea extract at 100 and 200mg per head, and more effectively than with green tea extract. OTPP delayed lymphatic triglyceride absorption at 20 mg/head, though (-)-epigallocatechin gallate (EGCG) did not do so at the same dose. OTPP also suppressed postprandial hypertriglyceridemia after administration of olive oil in mice. The area under the curve (AUC) of plasma triglycerides was significantly decreased, by 53% and 76%, in the 500 and 1,000 mg/ kg OTPP groups respectively, as compared with the control group. These results suggest that OTPP is responsible for the suppression of hypertriglyceridemia by ingestion of oolong tea.

DOI： 10.1271/bbb.60635

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3, 7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R,6S)-2,6-bis(3,4- dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, N -nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a] quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics. G

DOI： 10.1124/jpet.105.100149

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Fifty-four polyphenols isolated from tea leaves were evaluated for their inhibitory activities against pancreatic lipase, the key enzyme of lipid absorption in the gut. (-)-Epigallocatechin 3-O-gallate (EGCG), which is one of major polyphenols in green tea, showed lipase inhibition with an IC50 of 0.349 microM. Moreover, flavan-3-ol digallate esters, such as (-)-epigallocatechin-3,5-digallate, showed higher activities of inhibition on lipase with an IC50 of 0.098 microM. On the other hand, nonesterified flavan-3-ols, such as (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin, showed zero and/or the lowest activities against pancreatic lipase (IC50 > 20 microM). These data suggested that the presence of galloyl moieties within the structure was required for enhancement of pancreatic lipase inhibition. It is well-known that flavan-3-ols are polymerized by polyphenol oxidase and/or heating in a manufacturing process of oolong tea. Oolonghomobisflavans A and B and oolongtheanin 3'-O-gallate, which are typical in oolong tea leaves, showed strong inhibitory activities with IC50 values of 0.048, 0.108, and 0.068 microM, respectively, even higher than that of EGCG. The oolong tea polymerized polyphenols (OTPP) were prepared for the assay from oolong tea extract, from which the preparation effectively subtracted the zero and/or less-active monomeric flavan-3-ols by preparative high-performance liquid chromatography. The weight-average molecular weight (Mw) and number-average molecular-weight (Mn) values of OTPP were 2017 and 903, respectively, by using gel permeation choromatography. OTPP showed a 5-fold stronger inhibition against pancreatic lipase (IC50 = 0.28 microg/mL) by comparison with that of the tannase-treated OTPP (IC50 = 1.38 microg/mL). These data suggested that the presence of galloyl moieties within their chemical structures and/or the polymerization of flavan-3-ols were required for enhancement of pancreatic lipase inhibition.

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掲載種別：研究論文（学術雑誌）  

2-O-(β-D-Glucopyranosyl)ascorbic acid (AA2βG) isolated from a popular traditional Chinese food (Lycium fruit) was synthesized using cellulase derived from Trichoderma sp. with cellobiose as a glucose donor. 6-O-(β-D-Glucopyranosyl)ascorbic acid as well as AA2βG was also synthesized in this reaction. The vitamin C activity of AA2βG was also evaluated using inherently scorbutic (osteogenic disorder Shionogi [ODS]) rats. The rats were fed vitamin C-deficient food and water containing AA2βG for 21. AA2βG supported their growth and the level of vitamin C in tissues was moderately maintained. The vitamin C level in some tissues depended on the hydrolytic activity of AA2βG (β-glucosidase activity) although the correlation was not statistically significant (P=0.08). The results indicate that AA2βG has pro-vitamin C activity. © 2005, The Society for Biotechnology, Japan.

DOI： 10.1263/jbb.99.361

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the present study, we investigated the antioxidative effect of oolong tea in vitro and in vivo using the oxygen radical absorbance capacity (ORAC) assay. An oolong tea extract, catechin and related compounds suppressed the oxidation of fluorescence induced by AAPH in a dose-dependent manner, that is, they prolonged the antioxidant time in vitro. Oral administration of the oolong tea extract to mice treated with restraint stress increased ORAC activity in plasma as compared with a stress control group. The extract also increased plasma vitamin C levels, and there was a good relationship between ORAC activity and the vitamin C level in plasma. The elevation of plasma ORAC and vitamin C level may have been related to the stress-relieving effect of oolong tea. These effects are probably due to the antioxidative properties of the tea. Thus, these findings suggested that oolong tea has beneficial effects on health related to its antioxidative action.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A novel stable precursor of ascorbic acid (vitamin C), 2-O-(beta-D-glucopyranosyl)ascorbic acid, was isolated from both the ripe fresh fruit and dried fruit of Lycium barbarum L., a plant of the Solanaceae family. The chemical structure was inferred by instrumental analyses and confirmed by chemical synthesis. The dried fruit of Lycium barbarum L. contained ca. 0.5% of it, which is comparable to the ascorbic acid content of fresh lemons. It increased the blood ascorbic acid by oral administration to rats, and it was also detected in blood from the portal vein.

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掲載種別：研究論文（学術雑誌）  

Objectives: A randomized double-blind placebo-controlled crossover study was conducted on 22 subjects with borderline and mild hyperlipidemia to evaluate the suppressive effect of OTPP (oolong tea polymerized polyphenols) enriched oolong tea beverage on postprandial serum triglyceride elevation. Methods: Subjects were Japanese adult male and female whose serum triglyceride levels were between 100-250mg/dL. Subjects were divided into two groups randomly, and ingested a high fat meal (40 g fat) and test beverage (OTPP enriched oolong tea beverage or the placebo beverage). Serum triglyceride elevation was determined at 0, 1, 2, 3, 4, 5 hr after ingestion of the meal. Results: Postprandial serum triglyceride elevation was significantly suppressed at 3hr and 5hr after a high fat meal ingestion by taking OTPP enriched oolong tea beverage compared with the placebo beverage. Postprandial chylomicron elevation was also significantly decreased at 2hr, 3hr and 5hr after a high fat meal ingestion. Δ AUCs (areas under the curves) of both serum trigliceride and chylomicron levels were significantly decreased by 18.3% (p < 0.05) and 29.9% (p < 0.01), respectively. There were no significant differences in both LDL and total cholesterol levels. No adverse effects were observed in taking OTPP enriched oolong tea beverages. Conclusions: OTPP enriched oolong tea beverage has remarkable suppressive effect on the postprandial serum triglyceride elevation in the subjects with borderline and mild hyperlipidemia, suggesting that this beverage is useful for risk reduction of life-style related diseases.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In the present study, we investigated the anti-oxidant activity of oolong tea in an oxidation model using human low-density lipoprotein (LDL). Oolong tea suppressed the oxidation of LDL induced by 2-2'-azobis 4-methoxy-2,4-dimethyvaleronitrile (V70) in a dose-dependent manner, that is, it prolonged the lag time to 114.3%, 138% and 199.9% as compared with the control group at 0.5 microg/ml, 1.0 microg/ml, and 2.5 microg/ml, respectively. We also determined the scavenging effect of oolong tea on active oxygen radicals using the electron spin resonance (ESR) technique with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent. The intensity of the ESR signals for the DMPO-OOH adduct formed by the hypoxanthine/xanthine oxidase reaction system with DMPO decreased in the presence of oolong tea. The IC(50) of oolong tea was 19.9 microg/ml. These findings suggested that oolong tea has beneficial effects on health related to its anti-oxidative action.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We previously showed a prophylactic effect of Lactobacillus pentosus strain S-PT84 against oral candidiasis in mice. In the present study, we evaluated the protective effect of S-PT84 against Candida infection of the gastrointestinal tract. As the first step, we used an in vitro assay to compare the inhibitory effects of several lactobacilli (S-PT84 and Lactobacillus pentosus type strain JCM1558T, Lactobacillus gasseri type strain JCM1131T and Lactobacillus casei type strain JCM1134T) on mycelial growth of Candida albicans. S-PT84 directly adhered to Candida cells and showed the strongest growth-inhibitory activity among the tested Lactobacillus strains. In the second experiment, we used an in vivo assay to evaluate the effect of S-PT84 ingestion on severity score of stomach lesion and gastric inflammation in a mouse model of gastrointestinal candidiasis. The severity scores were significantly improved by oral administration of S-PT84 (6 mg/ 200 μL), consistent with decreased coverage of stomach lesions by patchy whitish plaques. The attenuation of stomach lesion severity by S-PT84 was more pronounced than that obtained with L. gasseri type strain JCM1131T, consistent with the results of the above in vitro study. Histological analysis also indicated that S-PT84 prevented the adhesion of C. albicans to the stomach surface and suppressed stomach inflammation caused by neutrophil infiltration. Furthermore, S-PT84 also suppressed the vascular permeability observed in Candida-infected stomach. These results suggest that oral administration of S-PT84 might be effective not only in inhibiting Candida infection but also in preventing gastric inflammation induced by Candida infection.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The effect of S-PT84, a heat-killed preparation of Lactobacillus pentosus on growth of Candida albicans was examined in vitro and in vivo. The mycelial growth was effectively inhibited by S-PT84 and seemed to bind to the hyphae. We assessed the potential of S-PT84 for treatment of oral and gastric candidiasis using a murine model. When 2 mg of S-PT84 was administered three times into the oral cavity of orally Candida infected mice, the score of lesions on the tongue was improved on day 2. When 50 μl and 200 μl of S-PT84 (10 mg/ml) were administered three times into the oral cavity (0.5 mg × 3) and the stomach (2 mg × 3) of the same mouse model, the number of viable Candida cells in the stomach was reduced significantly on day 2. These findings suggest the possibility that S-PT84 has potential as a food ingredient supporting anti-Candida treatment, especially for Candida infection in the gastrointestinal tract.

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Ireland Ltd  

DOI： 10.1016/j.neures.2010.10.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Splenic sympathetic nerve activity (SNA) modulates cellular immune functions such as splenic natural killer cell activity. Lactobacillus pentosus strain S-PT84 enhances splenic natural killer cell activity. Here, we examined whether S-PT84 affects splenic natural killer activity through splenic SNA in BALB/c mice. Splenic SNA was significantly decreased following the administration of S-PT84. This phenomenon was inhibited by pretreatment with thioperamide (histamine H3 receptor antagonist), suggesting that S-PT84 directly affected splenic SNA. Thioperamide also inhibited the increase in splenic natural killer activity by S-PT84. Thus, the change in splenic natural killer activity by S-PT84 may be partially modulated through SNA.

DOI： 10.1097/WNR.0000000000000036

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.mrgentox.2011.02.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

DOI： 10.1016/j.mrgentox.2010.10.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dihomo-gamma-linolenic acid (DGLA) is one of the essential fatty acids, and has anti-inflammatory and anti-allergic effects. To assess the toxicity of a novel DGLA oil produced by the fungus Mortierella alpina, we examined it in the Ames test and in acute and subchronic oral toxicity tests in rats. In the Ames test, no mutagenicity was found up to 5000 microg/plate. The acute toxicity test revealed no toxicity related to DGLA oil at 10 g/kg. In the subchronic toxicity test, DGLA oil (500, 1000, and 2000 mg/kg) was orally administered. Water and soybean oil (2000 mg/kg) were used for the no-oil control and soybean oil control groups, respectively. There was no death in either sex. Because of administration of large amounts of oil, food consumption was low in the soybean oil control and the three test groups, which appeared to mildly decrease urinary excretion of Na, K, and Cl, as well as total serum protein, albumin, and blood urea nitrogen levels. There were no toxicological changes in body weight, food consumption, ophthalmological examination, urinalysis, hematological examination, blood biochemical examination, necropsy, organ weight, or histopathological examination. These findings show that the no-observed-adverse-effect level of the DGLA oil was 2000 mg/kg.

DOI： 10.1016/j.fct.2009.03.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The first chemical synthesis of two metabolites ((1R,2S,5R,6S)-6-(3,4- dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane (SC-1) and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0] octane (SC-2)) of sesamin was achieved by a simple two-step approach from sesamin. The approach consists of acetoxylation of the methylenedioxy moiety(ies) with lead(IV) tetraacetate and acid hydrolysis of the resulting hemiorthoester to SC-1 and SC-2. © 2008 Pharmaceutical Society of Japan.

DOI： 10.1248/cpb.56.1611

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty acid composition. Wistar rats were fed with three kinds of oil for two weeks as follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver, serum, and brain of the DGLA group were higher than those of the GLA oil group. We also examined the dose effect of DGLA. The DGLA levels in the liver, serum, and brain significantly increased with increasing dosage of DGLA in the diet. DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat plasma. The mechanism for GLA administration to improve atopic eczema is thought to involve an increase in the concentration of DGLA metabolized from GLA, so these results suggest that the dietary effect of DGLA would be more dominant than GLA.

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掲載種別：研究論文（学術雑誌）  

To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, Fischer 344 rats were given an AA-supplemented powder diet for 12 weeks from 18.6 months old as part of the old AA (OA) group. Other age-matched rats were fed a non-AA-supplemented powder diet as part of the old control (OC) group, and young rats were fed lab pellets as part of the young control (YC) group. When the aged rats reached 20.0 months old, all animals were tested for spontaneous activity in an open field, followed by the Morris water maze place and cue tasks. Escape latencies for the place task showed that the YC rats were fastest, and there was no difference between the OA and OC groups. However, the probe test and the first block of the cue task indicated that the OA rats remembered the location of an invisible platform better than the OC rats. Although the amount of hippocampal AA was larger in the OA rats than in the OC rats, the difference was not significant. The results showed that AA administration to aged animals may alleviate age-related deficits in spatial cognition. © 2006 Japanese Psychological Association.

DOI： 10.1111/j.1468-5884.2006.00312.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, F-344 rats were administered with an AA-supplemented powder diet from 79 weeks of age (OA group). For comparison, we also used an age-matched control group of animals (OC group) that were fed with a non AA-supplemented powder diet. When the subjects reached 87 weeks old, they were trained for Morris water maze place and cue tasks. Escape latencies of the OA group on the place task were significantly shorter than those of the OC group in the latter half of training. The probe test showed that OA rats remembered the trained platform position significantly better than OC rats. In the cue task training, the OC group was significantly slower than the OA group at the beginning of training, but their performance soon matched with that of the OA group. Fatty acids in the hippocampi were measured after the behavioral testing. There was no difference in AA composition in hippocampal phospholipids between the OA and OC groups. However, regression analysis conducted on AA composition and place task performance showed a significant correlation between these two parameters. The present study suggests that AA administration to aged animals can alleviate age-related deficits in spatial cognition. © 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.physbeh.2005.02.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 μm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus. © 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/S0168-0102(03)00123-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study examined the hypoglycaemic activity of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) in ICR mice by oral glucose tolerance testing. The blood glucose level was significantly lower in the C. paliurus extract treatment group than in the control group after animals were given sucrose. This difference was not observed following the administration of glucose. We demonstrated that the chronological change in the level of blood glucose in genetically hyperglycemic obese KK-Ay mice is significantly lower when C. paliurus extract is administered daily for three weeks. An in vitro study showed that C. paliurus inhibits alpha-glucosidase, a disaccharide-degrading enzyme in the small intestinal mucosa, leading to a decrease in the absorption of glucose into the blood and a subsequent lowering of the blood glucose level.

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

DOI： 10.1080/15216540152035055

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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記述言語：日本語   出版者・発行元：日本ビタミン学会  

CiNii Article

CiNii Books

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J-GLOBAL

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開催年月日： 1996年

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開催年月日： 1996年

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開催年月日： 1995年

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開催年月日： 1995年

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開催年月日： 1994年

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開催年月日： 1993年

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