研究者紹介システム
| 福田 伊津子 |  |
| フクダ イツコ | |
| 大学院農学研究科 生命機能科学専攻 | |
| 助教 | |
| 農芸化学関係 |
研究者情報
所属
【主配置】
大学院農学研究科 生命機能科学専攻【配置】
農学部 生命機能科学科
学位
授業科目
- 食と健康Ｂ, 国際教養教育院, 2021
- 食と健康Ａ, 国際教養教育院, 2021
- 特定課題演習 I-1, 大学院農学研究科, 2021
- 課題開発演習, 大学院農学研究科, 2021
- 生命機能科学プレゼンテーション演習Ⅰ（オーラル・ペーパー）, 大学院農学研究科, 2021
- 特定課題演習 II-1, 大学院農学研究科, 2021
- 特定課題演習 I-2, 大学院農学研究科, 2021
- 生命機能科学プレゼンテーション演習Ⅱ（オーラル・ペーパー）, 大学院農学研究科, 2021
- 特定課題演習 II-2, 大学院農学研究科, 2021
- 食の安全科学実践検査学, 農学部, 2021
- 卒業研究, 農学部, 2021
- 応用生命化学基礎英語１, 農学部, 2021
- 分析化学Ａ, 農学部, 2021
- 応用生命化学基礎英語, 農学部, 2021
- 食の安全科学技術演習, 農学部, 2021
- 応用生命化学基礎英語２, 農学部, 2021
- 高度教養セミナー農学部応用生命化学入門, 農学部, 2021
- 高度教養セミナー農学部応用生命化学, 農学部, 2021
- 高度教養セミナー農学部応用生命化学, 農学部, 2021
- 応用生命化学実験I, 農学部, 2021
ジャンル
コメントテーマ
研究活動
研究キーワード
研究分野
受賞
2010年10月 日本生物工学会, 第18回生物工学論文賞, パン酵母β-グルカンのラットにおける脂質異常症予防効果
国内学会・会議・シンポジウム等の賞
2008年10月 日本栄養・食糧学会近畿支部, 日本栄養・食糧学会近畿支部若手奨励賞, 研究題目「芳香族炭化水素類によるアリール炭化水素受容体の活性化に対するカテキンの作用」
論文
- 2021年10月, 35 (4), 231 - 239, 日本語我が国の大学研究施設で飼育されている実験用マウスの糞便細菌叢の構成比較
[査読有り]
研究論文（学術雑誌）
We report the isolation of bacteria capable of degrading milk oligosaccharides from suckling infant rats. The bacteria were successfully isolated via a selective enrichment method, in which the serially diluted intestinal contents of infant rats were individually incubated in an enrichment medium containing 3'-sialyllactose (3'-SL), followed by the isolation of candidate strains from streaked agar plates and selection of 3'-SL-degrading strains using thin-layer chromatography. Subsequent genomic and phenotypic analyses identified all strains as Enterococcus gallinarum. The strains were capable of degrading both 3'-SL and 6'-SL, which was not observed with the type strain of E. gallinarum used as a reference. Furthermore, a time-course study combining high-performance anion-exchange chromatography with pulsed amperometric detection revealed that the representative strain AH4 degraded 3'-SL completely to yield an equimolar amount of lactose and an approximately one-fourth equimolar amount of sialic acid after 24 hr of anaerobic incubation. These findings point to a possibility that the enterococci degrade rat milk oligosaccharides to "cross-feed" their degradants to other members of concomitant bacteria in the gut of the infant rat.
2021年, Bioscience of microbiota, food and health, 40 (1), 27 - 32, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
We investigated bacteria that have a nutritional symbiotic relationship with respect to milk oligosaccharides in gut microbiota of suckling rats, with specific reference to sialyllactose (SL) degrading Enterococcus gallinarum. Our next generation sequencing analysis of the colonic contents of 12-day-old suckling rats revealed that almost half of the bacteria in the microbiota belonged to the Lactobacillaceae family. Major Lactobacillus species in the contents were identified as L. johnsonii, L. murinus, and L. reuteri. We then monitored changes in numbers of the above Lactobacillus species, E. gallinarum, and the bacteria belonging to the family Enterobacteriaceae (i.e., enterobacteria) in the colonic contents of infant rats at 7, 12, 21, 28, and 35 days of age by using real-time PCR assays targeting these bacterial groups. The 7-day-old infant rats had a gut microbiota in which enterobacteria were predominant. Such dominance was replaced by L. johnsonii and the concomitant E. gallinarum markedly increased in those of 12 and 21 days of ages. During this period, the number of enterobacteria declined dramatically, but that of L. reuteri surged dramatically. Our separate in vitro experiment showed that supplementation of culture media with SL promoted the growth of L. johnsonii and E. gallinarum, with marked production of lactic acid. These findings revealed possible milk oligosaccharide-mediated cross-feeding between E. gallinarum and L. johnsonii, with the former degrading SL to release lactose to be utilized by the latter.
2021年, Bioscience of microbiota, food and health, 40 (4), 204 - 211, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Extracellular proteins are important factors in host-microbe interactions; however, the specific factors that enable bifidobacterial adhesion and survival in the gastrointestinal (GI) tract are not fully characterized. Here, we discovered that Bifidobacterium longum NCC2705 cultured in bacterium-free supernatants of human fecal fermentation broth released a myriad of particles into the extracellular environment. The aim of this study was to characterize the physiological properties of these extracellular particles. The particles, approximately 50 to 80 nm in diameter, had high protein and double-stranded DNA contents, suggesting that they were extracellular vesicles (EVs). A proteomic analysis showed that the EVs primarily consisted of cytoplasmic proteins with crucial functions in essential cellular processes. We identified several mucin-binding proteins by performing a biomolecular interaction analysis of phosphoketolase, GroEL, elongation factor Tu (EF-Tu), phosphoglycerate kinase, transaldolase (Tal), and heat shock protein 20 (Hsp20). The recombinant GroEL and Tal proteins showed high binding affinities to mucin. Furthermore, the immobilization of these proteins on microbeads affected the permanence of the microbeads in the murine GI tract. These results suggest that bifidobacterial exposure conditions that mimic the intestine stimulate B. longum EV production. The resulting EVs exported several cytoplasmic proteins that may have promoted B. longum adhesion. This study improved our understanding of the Bifidobacterium colonization strategy in the intestinal microbiome.IMPORTANCE Bifidobacterium is a natural inhabitant of the human gastrointestinal (GI) tract. Morphological observations revealed that extracellular appendages of bifidobacteria in complex microbial communities are important for understanding its adaptations to the GI tract environment. We identified dynamic extracellular vesicle (EV) production by Bifidobacterium longum in bacterium-free fecal fermentation broth that was strongly suggestive of differing bifidobacterial extracellular appendages in the GI tract. In addition, export of the adhesive moonlighting proteins mediated by EVs may promote bifidobacterial colonization. This study provides new insight into the roles of EVs in bifidobacterial colonization processes as these bacteria adapt to the GI environment.
2020年09月17日, Applied and environmental microbiology, 86 (19), 英語, 国際誌[査読有り]
研究論文（学術雑誌）
Microbial production of butyrate is impaired in patients with ulcerative colitis (UC); however, this inhibition is not well understood in Japanese UC patients. Therefore, we quantitatively analyzed genes encoding butyryl-CoA:acetate CoA-transferase (but) and butyrate kinase (buk) in the gut microbiota of Japanese patients with UC and healthy volunteers (HVs). But showed higher levels than buk. Moreover, patients with UC showed significantly decreased levels of but associated with Roseburia sp./Eubacterium rectale compared with HVs. But, which is associated with Faecalibacterium sp., was maintained in patients with UC, with an unchanged relative abundance of Faecalibacterium sp. microorganisms in patients with UC compared with HVs.
2019年10月, Bioscience of Microbiota, Food and Health, 38 (4), 159 - 163, 英語, 国内誌[査読有り]
研究論文（学術雑誌）
Compositional alteration of the gut microbiota is associated with ulcerative colitis (UC). Here, a model culture system is established for the in vitro human colonic microbiota of UC, which will be helpful for determining medical interventions. 16S ribosomal RNA sequencing confirms that UC models are successfully developed from fecal inoculum and retain the bacterial species biodiversity of UC feces. The UC models closely reproduce the microbial components and successfully preserve distinct clusters from the healthy subjects (HS), as observed in the feces. The relative abundance of bacteria belonging to the family Lachnospiraceae significantly decreases in the UC models compared to that in HS, as observed in the feces. The system detects significantly lower butyrogenesis in the UC models than that in HS, correlating with the decreased abundance of Lachnospiraceae. Interestingly, the relative abundance of Lachnospiraceae does not correlate with disease activity (defined as partial Mayo score), suggesting that Lachnospiraceae persists in UC patients at a decreased level, irrespective of the alteration in disease activity. Moreover, the system shows that administration of Clostridium butyricum MIYAIRI restores butyrogenesis in the UC model. Hence, the model detects deregulation in the intestinal environment in UC patients and may be useful for simulating the effect of probiotics.
2019年, Biotechnology Journal, 14 (5), e1800555, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
This study investigated the effect of various prebiotics (indigestible dextrin, α-cyclodextrin, and dextran) on human colonic microbiota at a dosage corresponding to a daily intake of 6 g of prebiotics per person (0.2% of dietary intake). We used an in vitro human colonic microbiota model based on batch fermentation starting from a faecal inoculum. Bacterial 16S rRNA gene sequence analysis showed that addition of 0.2% prebiotics did not change the diversity and composition of colonic microbiota. This finding coincided with results from a clinical study showing that the microbiota composition of human faecal samples remained unchanged following administration of 6 g of prebiotics over seven days. However, compared to absence of prebiotics, their addition reduced the pH and increased the generation of acetate and propionate in the in vitro system. Thus, even at such relatively low amounts, prebiotics appear capable of activating the metabolism of colonic microbiota.
Nature Publishing Group, 2018年12月01日, Scientific Reports, 8 (1), Article number: 435, 英語[査読有り]
研究論文（学術雑誌）
Poly (ADP-ribose) polymerase family, member 1 (Parp1) has pleiotropic and disparate functions in multiple cellular signaling pathways through post-translational protein modification. It contributes to the regulation of various cellular processes, including DNA damage repair, cell death, and cell differentiation, genetically or epigenetically. Meanwhile, the functions of Parp1 in intercellular signaling remain to be established. To examine the functions of Parp1 in intercellular signaling, we examined microRNA (miRNA) regulation in exosomes derived from Parp1-deficient (Parp1-/-) embryonic stem (ES) cells. The percentages of miRNAs among total RNAs, including small RNAs such as miRNAs, snRNAs, snoRNAs, tRNAs, exonic RNAs, and intronic RNAs, in Parp1+/+ and Parp1-/- ES cell-derived exosomes were 8.2% and 3.5%, respectively. Overall, 329 distinct miRNAs exhibited ≥2-fold changes (118 upregulated; 211 downregulated). The upregulated miRNAs targeted 810 candidate genes, and the downregulated miRNAs targeted 716 candidate genes. Pathway analyses revealed that the upregulated miRNAs were significantly associated with five pathways including MAPK signaling cascades (p < 0.05), indicating that the target genes in these pathways were suppressed in Parp1-/- ES cells. In quantitative analyses of miRNA expression, miR365-3p, let-7a-5p, miR196b-5p, miR203-3p, miR98-5p, and miR146a-5p were increased by ≥ 2-fold in Parp1-/- ES cell-derived exosomes. Gene ontology enrichment analyses revealed that the upregulated miRNAs were significantly annotated for growth and stress-related cell signaling and cell communication (p < 0.05). Parp1 deficiency in ES cells led to inhibition of cell-cell communication, possibly by intercellular signal transduction, suggesting that Parp1 functions extracellularly by regulating exosomal miRNAs.
2018年05月15日, Biochemical and biophysical research communications, 499 (3), 410 - 415, 英語, 国際誌研究論文（学術雑誌）
Accumulating evidence suggests that dietary taurine (2-aminoethanesulfonic acid) exerts beneficial anti-inflammatory effects in the large intestine. In this study, we investigated the possible impact of taurine on human colonic microbiota using our single-batch fermentation system (Kobe University Human Intestinal Microbiota Model; KUHIMM). Fecal samples from eight humans were individually cultivated with and without taurine in the KUHIMM. The results showed that taurine remained largely undegraded after 30 h of culturing in the absence of oxygen, although some 83% of the taurine was degraded after 30 h of culturing under aerobic conditions. Diversity in bacterial species in the cultures was analyzed by 16S rRNA gene sequencing, revealing that taurine caused no significant change in the diversity of the microbiota; both operational taxonomic unit and Shannon-Wiener index of the cultures were comparable to those of the respective source fecal samples. In addition, principal coordinate analysis indicated that taurine did not alter the composition of bacterial species, since the 16S rRNA gene profile of bacterial species in the original fecal sample was maintained in each of the cultures with and without taurine. Furthermore, metabolomic analysis revealed that taurine did not affect the composition of short-chain fatty acids produced in the cultures. These results, under these controlled but artificial conditions, suggested that the beneficial anti-inflammatory effects of dietary taurine in the large intestine are independent of the intestinal microbiota. We infer that dietary taurine may act directly in the large intestine to exert anti-inflammatory effects.
2017年, PloS one, 12 (7), e0180991, 英語, 国際誌[査読有り]
研究論文（学術雑誌）
We devised a single-batch fermentation system to simulate human colonic microbiota from fecal samples, enabling the complex mixture of microorganisms to achieve densities of up to 1011 cells/mL in 24 h. 16S rRNA gene sequence analysis of bacteria grown in the system revealed that representatives of the major phyla, including Bacteroidetes, Firmicutes, and Actinobacteria, as well as overall species diversity, were consistent with those of the original feces. On the earlier stages of fermentation (up to 9 h), trace mixtures of acetate, lactate, and succinate were detectable; on the later stages (after 24 h), larger amounts of acetate accumulated along with some of propionate and butyrate. These patterns were similar to those observed in the original feces. Thus, this system could serve as a simple model to simulate the diversity as well as the metabolism of human colonic microbiota. Supplementation of the system with several prebiotic oligosaccharides (including fructo-, galacto-, isomalto-, and xylo-oligosaccharides; lactulose; and lactosucrose) resulted in an increased population in genus Bifidobacterium, concomitant with significant increases in acetate production. The results suggested that this fermentation system may be useful for in vitro, preclinical evaluation of the effects of prebiotics prior to testing in humans.
PUBLIC LIBRARY SCIENCE, 2016年08月, PLOS ONE, 11 (8), e0160533, 英語[査読有り]
研究論文（学術雑誌）
Polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) develop various adverse effects through activation of an aryl hydrocarbon receptor (AhR). The suppressive effects of brewed green tea and black tea on 3-methylcholanthrene (MC)-induced AhR activation and its downstream events were examined in the liver of rats. Ad-libitum drinking of green tea and black tea suppressed MC-induced AhR activation and elevation of ethoxyresorufin O-deethylase activity in the liver, whereas the teas themselves did not induce them. Tea showed a suppressive fashion on the expression of cytochrome P450 1A1 (CYP1A1). Tea suppressed the AhR activation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) ex vivo. A part of catechins and theaflavins was present in plasma and liver as conjugated and intact forms. The results of this study suggested that active component(s) of tea are incorporated in the liver and suppress the activity of CYP1As through the AhR activation pathway.
INFORMA HEALTHCARE, 2015年05月, INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION, 66 (3), 300 - 307, 英語[査読有り]
研究論文（学術雑誌）
- 2015年, International Journal of Food Sciences and Nutrition, 66, 300 - 307, 英語Catechins in tea suppress the expression and activity of cytochrome P450 1A1 through the aryl hydrocarbon receptor activation pathway in rat livers
[査読有り]
研究論文（学術雑誌）
Carcinogenicity induced by phase I and phase II drug-metabolizing enzymes (DMEs) involves the following: certain procarcinogens are metabolized and activated into carcinogens by phase I CYPs or phase II GSTs, and the resultant carcinogens bind with biological macromolecules this is an initiation step of carcinogenicity. Conversely, multidrug resistance is caused by an overexpression of transporters excreting chemotherapeutic agents in cancer cells. Naturally occurring polyphenols have been reported to possess anticancer effects. In this review, strategies for preventing carcinogenicity involving DMEs and transporters by polyphenols are discussed. Regarding DMEs, the balance of phase I and phase II enzymes is important for preventing carcinogenicity, and tea polyphenols, flavonoids, curcumin and resveratrol are candidates for suppressing tumorigenesis. Tea polyphenols, flavonoids, resveratrol, tannic acid, and curcumin all inhibit, or modulate, ABC transporters, and could prevent multidrug resistance in cancer cells. © 2014 Elsevier Inc. All rights reserved.
Elsevier Inc., 2013年11月, Polyphenols in Human Health and Disease, 2, 1127 - 1135, 英語[査読有り]
論文集(書籍)内論文
- 2013年, Organohalogen Compounds, 75, 620 - 624, 英語
[査読有り]
研究論文（国際会議プロシーディングス）
- New Structure Descriptor in the Structure-Activity Relationship Study on the Suppression of Aryl Hydrocarbon Receptor Transformation by Anthraquinones
A new descriptor showing the positions of functional groups in compounds with the same main backbone was developed. This descriptor was applied to the Quantitative Structure-Activity Relationship (QSAR) study on the suppression activities of anthraquinones via transformation of the aryl hydrogen receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. It was shown that the newly developed descriptor played an important role in the QSAR study.
KARGER, 2012年03月, FOOD SCIENCE AND TECHNOLOGY RESEARCH, 18 (2), 173 - 176, 英語[査読有り]
研究論文（学術雑誌）
- 2012年, Organohalogen Compounds, 74, 1005 - 1008, 英語Induction of the multidrug-resistant Mdr1b mediated by aryl hydrocarbon receptor in mouse hepatoma Hepa-1c1c7 cells
研究論文（学術雑誌）
- 2012年, Organohalogen Compounds, 74, 173 - 176, 英語Application of a southwestern-chemistry based ELISA to evaluation of dioxins in the farm products
研究論文（学術雑誌）
Black soybean (Glycine max) has been used for traditional medicine and food in Asian countries, but safety of its hull has not been studied. We conducted acute and chronic oral toxicity studies. For the acute study, an extract of black soybean hull (BE; 2.5 g/kg body weight) was administered singly by intragastric intubation to Sprague-Dawley rats and C57BL/6 mice. There was no death or significant decrease in body weight in rats and mice, and the oral LD50 of BE was >2.5 g/kg body weight. In the chronic study, BE was administered at dietary levels of 0% (control), 2.0%, and 5.0% to male and female C57BL/6 mice for 26 weeks. No mortality or toxicologically significant clinical changes were observed through the experimental period. Although body weights, as well as abdominal fat, blood levels of triglyceride and total cholesterol in 5.0% males were significantly lower than that in control and 2.0% groups, these changes were considered not to be adverse. Hematology and histopathological observation revealed no toxicologically significant changes. The no-observed adverse-effect-level of BE was estimated to be 5.0% in the diet (5074.1 mg/kg body weight/day for males and 7617.9 mg/kg body weight/day for females). (C) 2011 Elsevier Ltd. All rights reserved.
PERGAMON-ELSEVIER SCIENCE LTD, 2011年12月, FOOD AND CHEMICAL TOXICOLOGY, 49 (12), 3272 - 3278, 英語[査読有り]
研究論文（学術雑誌）
Glucose transporter-4 (GLUT4) is a transmembrane protein that plays a major role in insulin-mediated glucose transport in muscle and adipocytes. For glucose transport to occur, the GLUT4 protein needs to be translocated from the intracellular pool to the plasma membrane, and certain compounds may enhance this process. The present study investigated the promotion of glucose uptake in differentiated L6 myotubes by cardamonin, isolated from Alpinia katsumadai. Cardamonin increased translocation of GLUT4 to the plasma membrane in L6 cells, but did not activate protein kinase C zeta/lambda, Akt, or AMP-activated protein-kinase, all of which are known to regulate GLUT4 translocation. The glucose-uptake-promoting activity of cardamonin was not lowered by treatment with a phosphatidylinositol 3'-kinase inhibitor. These results suggest that cardamonin is a promising active compound for maintaining glucose homeostasis, and that it acts via an unknown mechanism that does not involve activation of the downstream insulin signal and AMP-activated protein kinase. Copyright (C) 2011 John Wiley & Sons, Ltd.
WILEY-BLACKWELL, 2011年08月, PHYTOTHERAPY RESEARCH, 25 (8), 1218 - 1224, 英語[査読有り]
研究論文（学術雑誌）
Black soybean seed coat extract (BE) is a polyphenol-rich food material consisting of 9.2% cyanidin 3-glucoside, 6.2% catechins, 39.8% procyanidins, and others. This study demonstrated that BE ameliorated obesity and glucose intolerance by up-regulating uncoupling proteins (UCPs) and down-regulating inflammatory cytokines in C57BL/6 mice fed a control or high-fat diet containing BE for 14 weeks. BE suppressed fat accumulation in mesenteric adipose tissue, reduced the plasma glucose level, and enhanced insulin sensitivity in the high-fat diet-fed mice. The gene and protein expression levels of UCP-1 in brown adipose tissue and UCP-2 in white adipose tissue were up-regulated by BE. Moreover, the gene expression levels of major inflammatory cytokines, tumor necrosis factor-a and monocyte chemoattractant protein-1 were remarkably decreased by BE in white adipose tissue. BE is a beneficial food material for the prevention of obesity and diabetes by enhancing energy expenditure and suppressing inflammation.
AMER CHEMICAL SOC, 2011年08月, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 59 (16), 8985 - 8993, 英語[査読有り]
研究論文（学術雑誌）
We developed a new process for enzymatically synthesized glycogen (ESG), which is equivalent in physicochemical properties to natural-source glycogen (NSG) except its resistant property to degradation by alpha-amylase in vitro. In this study the metabolic fates of orally administered ESG in rats were investigated by a single oral administration test and a 2 week ingestion test. The glycemic index of ESG was 79. After the 2 week ingestion of ESG, the cecal content and production of short chain fatty acids were significantly increased, the pH value of cecal content was lowered, and the counts of Bifidobacterium and Lactobacillus in feces were significantly increased. Additionally, plasma levels of triacylglycerol and total cholesterol were significantly reduced by ESG. In contrast, NSG did not affect these parameters at all. The results collectively suggest that around 20% of orally administered ESG was transferred to the cecum in the form of polymer and assimilated into short chain fatty acids by microbiota and the polymer affected lipid metabolism.
ROYAL SOC CHEMISTRY, 2011年04月, FOOD & FUNCTION, 2 (3-4), 183 - 189, 英語[査読有り]
研究論文（学術雑誌）
Scope: Glucose uptake in skeletal muscle is crucial for glucose homeostasis. Methods and results: Insulin and muscle contraction increase glucose uptake accompanied by the translocation of glucose transporter (GLUT) 4. In a search for promising foods, which can increase glucose uptake in skeletal muscle, we screened for active polyphenols by assaying for uptake of 2-deoxyglucose (2DG) in rat L6 muscle cells. Among 37 compounds, 4-hydroxyderricin and xanthoangelol, prenylated chalcones abundant in Ashitaba (Angelica keiskei Koidzumi, family Apiaceae), significantly increased 2DG uptake in L6 cells by 1.9-fold at 10 mu M, compared with the level in DMSO-treated control cells. Next, we investigated the effect of these chalcones on the translocation of GLUT4 and its underlying mechanisms. The chalcones increased the GLUT4 level in the plasma membrane of L6 cells, but activated neither protein kinase C zeta/lambda, Akt, nor adenosine monophosphate-activated protein kinase, all of which regulate the GLUT4 translocation. Interestingly, the oral administration of a titrated chalcone-enriched Ashitaba extract containing 150.6 mg/g (dry base) of 4-hydroxyderricin and 146.0 mg/g (dry base) of xanthoangelol suppressed acute hyperglycemia in oral glucose tolerance tests of mice. Conclusions: Ashitaba is a promising functional food for the maintenance of the blood glucose level by inducing skeletal muscle-associated glucose uptake.
WILEY-BLACKWELL, 2011年03月, MOLECULAR NUTRITION & FOOD RESEARCH, 55 (3), 467 - 475, 英語[査読有り]
研究論文（学術雑誌）
Artemisia princeps is commonly used as a food ingredient and in traditional Asian medicine. In this study, we examined the effects of long-term administration of an ethanol extract of A. princeps (APE) on body weight, white adipose tissue, blood glucose, insulin, plasma and hepatic lipids, and adipocytokines in C57BL/6 mice fed a high-fat diet. Daily feeding of a 1% APE diet for 14 weeks normalized elevated body weight, white adipose tissue, and plasma glucose and insulin levels, and delayed impaired glucose tolerance in mice a fed high-fat diet. These events were not observed in mice fed a control diet containing 1% APE. Liver triglyceride and cholesterol levels were similar in mice fed a 1% APE-diet and those fed a control diet. In the high-fat diet groups, APE inhibited hepatic fatty acid synthase (FAS) and suppressed the elevation of plasma leptin, but had no effect on adiponectin levels. These findings suggest that the regulation of leptin secretion by APE may inhibit FAS activity with subsequent suppression of triglyceride accumulation in the liver and adipose tissues. Inhibition of lipid accumulation can, in turn, lead to improvements in impaired glucose tolerance.
ROYAL SOC CHEMISTRY, 2011年01月, FOOD & FUNCTION, 2 (1), 45 - 52, 英語[査読有り]
研究論文（学術雑誌）
- 2011年, Food and Chemical Toxicology, 49, 3272 - 3278, 英語Acute and chronic oral toxicity studies of black soybean (Glycine max) hull extract in mice and rats
[査読有り]
研究論文（学術雑誌）
- 2010年11月, Food & function, 1 (2), 167 - 173
[査読有り]
In this study, we investigated the effects of tea catechins on the translocation of glucose transporter (GLUT) 4 in 3T3-L1 adipocytes. We found that the ethyl acetate fraction of green tea extract, containing abundant catechins, most decreased insulin-induced glucose uptake activity in 3T3-L1 cells. When the cells were treated with 50 μM catechins in the absence or presence of insulin for 30 min, nongallate-type catechins increased glucose uptake activity without insulin, whereas gallate-type catechins decreased insulin-induced glucose uptake activity. (-)-Epicatechin (EC) and (-)-epigallocatechin (EGC), nongallate-type catechins, increased glucose uptake activity in the dose- and time-dependent manner, whereas (-)-catechin 3-gallate (Cg) and (-)-epigallocatechin 3-gallate (EGCg), gallate-type catechins, decreased insulin-induced glucose uptake activity in the dose- and time-dependent manner. When the cells were treated with 50 μM catechins for 30 min, EC and EGC promoted GLUT4 translocation, whereas Cg and EGCg decreased the insulin-induced translocation in the cells. EC and EGC increased phosphorylation of PKCλ/ζ without phosphorylation of insulin receptor (IR) and Akt. Wortmannin and LY294002, inhibitors for phosphatidylinositol 3′-kinase (PI3K), decreased EC- and EGC-induced glucose uptake activity in the cells. Cg and EGCg decreased phosphorylation of PKCλ/ζ in the presence of insulin without affecting insulin-induced phosphorylation of IR, and Akt. Therefore, EC and EGC promote the translocation of GLUT4 through activation of PI3K, and Cg and EGCg inhibit insulin-induced translocation of GLUT4 by the insulin signaling pathway in 3T3-L1 cells. © The Royal Society of Chemistry 2010.
2010年11月, Food and Function, 1 (2), 167 - 173, 英語[査読有り]
研究論文（学術雑誌）
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates biological and toxicological effects by binding to its agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Previously we demonstrated that flavonoids suppressed the TCDD-induced DNA-binding activity of the AhR in a structure-dependent manner. In this study, we investigated the mechanisms by which flavonoids suppressed the AhR-mediated signal transduction in mouse hepatoma Hepa-1c1c7 cells. Flavones and flavonols suppressed the TCDD-induced nuclear translocation of the AhR and dissociation of its partner proteins, heat shock protein 90 and X-associated protein 2, whereas flavanones and catechins did not. Flavonoids of all these four subclasses suppressed the phosphorylation of both AhR and Arnt and the formation of a heterodimer consisting of these proteins. Since certain flavonoids are known to inhibit mitogen-activated protein kinases (MAPKs), we confirmed the contribution of MAPK/ERK kinase (MEK) to the AhR-mediated signal transduction by using U0126, an inhibitor of MEK1/2. U0126 suppressed TCDD-induced phosphorylation of the AhR and Arnt followed by the DNA-binding activity of the AhR. Flavanones and catechins suppressed the TCDD-induced phosphorylation of ERK1/2. The inhibition of MEK/ERK phosphorylation is one of the mechanisms by which flavanones and catechins suppress the AhR-mediated signal transduction in Hepa-1c1c7 cells. (C) 2010 Elsevier Inc. All rights reserved.
ELSEVIER SCIENCE INC, 2010年09月, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 501 (1), 134 - 141, 英語[査読有り]
研究論文（学術雑誌）
- 2010年07月, Proceedings of the 15th meeting of International Humic Substances Society, Puerto de la Curz, Spain, 3, 182 - 185, 英語Sorption of pharmaceuticals to humic substances
[査読有り]
研究論文（国際会議プロシーディングス）
Upon binding to ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) is activated to form a heterodimer with an aryl hydrocarbon receptor nuclear translocator (Arnt). This complex binds to DNA. It has been shown that the AhR bonds to a DNA sequence called the dioxin response element (DRE), which controls the expression of battery genes. It is reported that TCDD releases arachidonic acid from membrane phospholipids via activation of phospholipase A(2)s (PLA(2)s) in various cell types. Recently, we demonstrated that the TCDD-activated AhR binds to the second intron of the Pla2g4a gene, which encodes cytosolic phospholipase A(2)alpha (cPLA(2)alpha), in mouse hepatoma Hepa-1c1c7 cells. This result suggests that Pla2g4a appears to be a target gene of the AhR. In the present study, we investigated whether the transcriptional regulation of Pla2g4a is dependent on the AhR in Hepa-1c1c7 cells. Treatment of the cells with TCDD increased mRNA expression of Pla2g4a and enzymatic activity of PLA(2). while this increased expression was not observed in AhR-defective c12 cells. After transient transfection of an Ahr gene-expressing plasmid into the 02 cells, expression of Pla2g4a was increased by TCDD. These results indicate that Pla2g4a may be a novel target gene of the AhR, and its transcriptional induction is mediated through binding of the AhR to the second intron of Pla2g4a, although this target site does not have a typical DRE sequence. (C) 2009, The Society for Biotechnology, Japan. All rights reserved.
SOC BIOSCIENCE BIOENGINEERING JAPAN, 2009年10月, Journal of Bioscience and Bioengineering, 108 (4), 277 - 281, 英語[査読有り]
研究論文（学術雑誌）
The suppression of cytochrome P450 1A1 (CYP1A1) expression was examined in mouse hepatoma Hepa-1c1c7 cells treated with serum prepared from (-)-epigallocatechin-3-gallate- and green tea extract-administered rats. Catechins were found in the rat plasma after the administration. In Hepa-1c1c7 cells, 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 expression was suppressed by treatment with the rat serum. It is concluded that catechins can possibly modulate CYP1A1 expression.
TAYLOR & FRANCIS LTD, 2009年05月, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 73 (5), 1206 - 1208, 英語[査読有り]
研究論文（学術雑誌）
Anthraquinones are widely present in plant kingdom, and clinically used as laxatives. Environmental contaminants, dioxins, develop various adverse effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We investigated the effects of 18 anthraquinones and 7 of their structurally related compounds on transformation of the AhR estimated by its DNA-binding activity in the cell-free system. 1,4-Dihydroxyanthraquinone (quinizarin), 1,5-dihydroxyanthraquinone (anthrarufin), 1,8-dihydroxyanthraquinone (danthron), and 5-hydroxy-1,4-naphthoquinone (juglone) strongly suppressed DNA-binding activity of the AhR induced by 0.1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with their IC(50) values around 1 mu M. On the other hand, anthraquinone, 2,6-dihydroxyanthraquinone (anthraflavic acid), and 2-hydroxy-1,4-naphthalendione (lawsone) showed moderate effects. Quantitative structure-activity relationships analysis demonstrated that hydroxyl groups at C1 or C4 but not C3 position of anthraquinone structure are critical for the suppressive effects. In addition, all compounds except lawsone had no agonistic effect. The suppressive effects of anthraquinones in a cultured cell system were also confirmed. In human hepatoma HepG2 cells, chrysophanol, danthron, and rhein also suppressed the DNA-binding activity in a dose-dependent manner, although aloe-emodin showed a moderate effect. The findings of this study may be useful for the design of the novel antagonists of the AhR. (C) 2008, The Society for Biotechnology. Japan. All rights reserved.
SOC BIOSCIENCE BIOENGINEERING JAPAN, 2009年03月, JOURNAL OF BIOSCIENCE AND BIOENGINEERING, 107 (3), 296 - 300, 英語[査読有り]
研究論文（学術雑誌）
- パン酵母β-グルカン摂取によるラットの盲腸内容物および糞便排泄に及ぼす影響
食物繊維不足は消化管疾患をもたらすことが知られている.本研究では,精製したパン酵母由来β-グルカン(BBG)によるラット盲腸内容物および糞排泄に及ぼす影響をセルロース(CE)を対照繊維として用いて比較検討した.BBGまたはCEを1%,3%,5%となるようAIN-93M粉末食に混合し,これらと無繊維食をラットに4週間自由摂取させた.盲腸組織重量は5%BBG食摂取群で5%CE食摂取群と比較して有意に増加し,一方で,盲腸内容物のpHは有意に低下した.ラット盲腸内容物中の酢酸,プロピオン酸,n-酪酸は5%BBG食摂取群で5%CE食摂取群と比較して有意に増加したことから,これらの短鎖脂肪酸の増加が盲腸内容物のpH低下に寄与していることが示唆された.さらに,糞の水分含量も5%BBG食摂取群で5%CE食摂取群と比較して有意に増加したことから,BBGは盲腸内発酵を促進して大腸管腔の水分保持に寄与することが示唆された.以上のことから,BBGは腸機能を調節することで便秘の抑制効果を発揮すること,およびその効果はCEよりすぐれていることが明らかとなった.
日本生物工学会, 2009年, 生物工学会誌, 87 (4), 170 - 174, 日本語[査読有り]
研究論文（学術雑誌）
- 2009年, 生物工学会誌, 87 (3), 129 - 134, 日本語パン酵母β-グルカンのラットにおける脂質異常症予防効果
[査読有り]
研究論文（学術雑誌）
- High-throughput evaluation of aryl hydrocarbon receptor-binding sites selected via chromatin immunoprecipitation-based screening in Hepa-1c1c7 cells stimulated with 2,3,7,8-tetrachlorodibenzo-p-dioxin
Upon binding to ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) is activated to form a heterodimer with an aryl hydrocarbon receptor nuclear translocator (Arnt) and binds to DNA. It has been shown that the binding of AhR to DNA depends on the dioxin response element (DRE) and controls xenobiotic-response genes. AhR-binding DNA fragments from mouse hepatoma Hepa-1c1c7 cells stimulated with TCDD were once enriched in a chromatin immunoprecipitation (ChIP) DNA library and screened through a high-throughput southwestern chemistry-based enzyme-linked immunosorbent assay (SW-ELISA). After screening 1,700 fragments, the ChIP-SW-ELISA screening strategy allowed us to isolate 77 fragments tightly interacting with AhR in the presence of TCDD. Only 39 of the 77 fragments appeared to contain a typical DRE, indicating that in some cases the DRE was dispensable for AhR-binding, while 75 fragments were located within promoter-distal regions. Genomic mapping of the 77 fragments enabled us to estimate 121 potential AhR targets including known targets such as Cyp1A1 and Cyp1B1, but only a limited number exhibited an altered expression dependent on TCDD. This study revealed the fact that TCDD-activated AhR frequently binds to promoter-distal regions even without a DRE and is not always involved in transcriptional regulation, suggesting that within the genome DNA-binding of AhR could take place often in many regions without cis-regulatory elements and might not be a key determinant to establish its regulatory function.
GENETICS SOC JAPAN, 2008年12月, GENES & GENETIC SYSTEMS, 83 (6), 455 - 468, 英語[査読有り]
研究論文（学術雑誌）
In this study, We investigated whether epigallocatechin gallate (EGCg) affects glucose uptake activity and the translocation Of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle. A single oral administration of EGCg at 75 mg/kg body weight promoted GLUT4 translocation in skeletal muscle of rats. EGCg significantly increased glucose uptake accompanying GLUT4 translocation in L6 myotubes at 1 nM. The translocation of GLUT4 was also observed both in skeletal muscle of mice and rats ex vivo and in insulin-resistant L6 myotubes. Wortmannin, an inhibitor of phosphatidylinositol 3'-kinase, inhibited both EGCg- and insulin-increased glucose uptakes, while genistein, an inhibitor of tyrosine kinase, failed to inhibit the EGC-increasecl uptake. Therefore, ECCg may improve hyperglycemia by promoting GLUT4 translocation in skeletal muscle with partially different mechanism from insulin. (C) 2008 Elsevier Inc. All rights reserved.
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008年12月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 377 (1), 286 - 290, 英語[査読有り]
研究論文（学術雑誌）
Dioxins enter the body through the diet and cause various toxicological effects through transformation of an aryl hydrocarbon receptor (AhR). Plant extracts and phytochemicals including flavonoids are reported to suppress this transformation. This paper investigates the suppression by a cacao polyphenol extract (CPE) of AhR transformation in vivo. The CPE was administered orally to C57BL/6 mice at 100 mg/kg of body weight, followed 1 h later by 3-methylcholanthrene (MC), an AhR agonist, injected intraperitoneally at 10 mg/kg of body weight. CPE suppressed the MC-induced transformation to the control level by inhibiting the formation of a heterodimer between AhR and an aryl hydrocarbon receptor nuclear translocator in the liver at 3 h postadministration. It also suppressed MC-induced cytochrome P4501A1 expression and NAD(P)H:quinone-oxidoreductase activity, whereas it increased glutathione S-transferase activity at 25 h. CPE constituents and their metabolites might contribute, at least in part, to the suppression of AhR transformation. The results indicate that the intake of CPE suppressed the toxicological effects of dioxins in the body.
AMER CHEMICAL SOC, 2008年11月, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 56 (21), 10399 - 10405, 英語[査読有り]
研究論文（学術雑誌）
Dioxins develop various adverse effects through transformation of the aryl hydrocarbon receptor (AhR). Since dioxins invade the body mainly with diet, it is important to search for AhR antagonists from a dietary source. Our findings have demonstrated that the suppressive effects of flavonoids on AhR transformation was classified into their subclasses with the following order flavones = flavonols = theaflavins > flavanones > catechins > isoflavones and anthocyans. Regarding flavonols, the competitive ligand binding analysis revealed that kaempferol, quercetin, and galangin inhibited the specific binding between the AhR and its agonist, 3-methylcholanthrene (MC) in a dose-dependent manner, indicating that at least flavonols acts as competitive antagonists of the AhR. These results suggest that the mechanisms by which flavonoids suppress AhR transformation differs in their subclasses. © 2008 American Chemical Society.
American Chemical Society, 2008年09月19日, ACS Symposium Series, 993, 369 - 374, 英語[査読有り]
研究論文（国際会議プロシーディングス）
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has multiple toxic effects causing a wasting syndrome characterized by a loss of body weight accompanied by a decrease in adipose tissue weight. To elucidate the mechanism behind this syndrome, we investigated the changes in lipid metabolism 7 and 21 days after a single intraperitoneal injection of TCDD at 1 mu g/kg body weight to male guinea pigs. TCDD caused the symptoms of the syndrome, body weight loss with a decrease in adipose tissue weight, while it increased the levels of triacylglycerols, total cholesterols, and free fatty acids in plasma. On day 7, TCDD decreased the levels of CCAAT/enhancer binding protein (C/EBP) alpha, peroxisome proliferator activated receptor gamma, and glucose transporter 4, adipogenesis-related factors, in adipose tissue, whereas the levels of retinoid X receptor a, C/EBP, C/EBP6, and c-Myc remained unchanged. TCDD also reduced the levels of both p125 precursor and p68 active forms of sterol regulatory element binding protein (SREBP)-1 and -2, the lypogenesis-related factors, and downregulated their DNA binding activity in adipose tissue, while it raised the levels of their p68 active forms and increased their DNA binding activity in the liver. TCDD decreased mRNA and protein levels of acetyl-CoA carboxylase and HMG-CoA synthase in the liver and adipose tissue. Similar results were obtained on day 21. These results suggest that TCDD disrupts lipid metabolism through changes in the expression levels of the adipogenesis-related and lipogenesis-related proteins in the liver and adipose tissue, and SREBPs would be involved in the development of the wasting syndrome. (c) 2008 Elsevier Inc. All rights reserved.
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2008年06月, TOXICOLOGY AND APPLIED PHARMACOLOGY, 229 (3), 281 - 289, 英語[査読有り]
研究論文（学術雑誌）
Halogenated and polycyclic aromatic hydrocarbons, exogenous ligands of the aryl hydrocarbon receptor (AhR), cause various toxicological effects through the transformation of the AhR. In this study, we investigated the antagonistic effects of indigoids on the transformation in addition to their agonistic ones. In a cell-free system, indigoids induced the transformation dose-dependently, but suppressed the transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the binding of 3-methyleholanthrene to the AhR. In mouse hepatoma Hepa-1clc7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYPIAI by inhibiting the translocation of AhR into the nucleus. When orally administered to mice at 10 mg/kg BW/day for three successive days, indigoids did not induce AhR transformation and expression of the CYPIA subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity. These results indicate that indigoids are able to bind to the AhR as ligands and exhibit antagonistic effects at lower concentrations in mammalian cells. (c) 2007 Elsevier Inc. All rights reserved.
ELSEVIER SCIENCE INC, 2008年02月, ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 470 (2), 187 - 199, 英語[査読有り]
研究論文（学術雑誌）
- 2008年, Journal of Clinical Biochemistry and Nutrition, 43(Suppl.1), 460 - 463, 英語Suppressive effects of propolis extract on cytochrome P4501A1 expression induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin
[査読有り]
研究論文（学術雑誌）
- 2008年, Journal of Clinical Biochemistry and Nutrition, 43(Suppl.1), 243-246, 英語Effect of chamomile extract on adiposity in mice fed a high-fat diet
[査読有り]
研究論文（学術雑誌）
Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines. (c) 2007 Elsevier Inc. All rights reserved.
PERGAMON-ELSEVIER SCIENCE LTD, 2007年12月, BIOCHEMICAL PHARMACOLOGY, 74 (11), 1619 - 1627, 英語[査読有り]
研究論文（学術雑誌）
Flavonoids have been reported to be dietary antagonists of an aryl hydrocarbon receptor (AhR). However, little is known about the molecular mechanism on their antagonistic effects. In this study, the inhibitory effect of flavonoids on ligand binding to the AhR and interaction between flavonoids and the AhR complex (AhRc) were investigated in each flavonoid subclass. Flavone, flavonol, and flavanone but not catechin inhibited the specific binding between the AhR and 3-methylcholanthrene dose-dependently, indicating that the former three subclasses possibly act as competitive antagonists of the AhR. However, catechin in addition to the former three subclasses directly interacted with the AhRc by surface plasmon resonance analysis. The dissociation constant values showed an inverse correlation with the suppressive effect on the DNA binding activity. These results suggest that flavone, flavonol, and flavanone act as competitive antagonists of the AhR, while catechin associates with the AhRc and indirectly exhibits its antagonistic effects. (c) 2007 Elsevier Inc. All rights reserved.
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2007年08月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 359 (3), 822 - 827, 英語[査読有り]
研究論文（学術雑誌）
Since the toxicological effects of dioxins are mainly mediated by the aryl hydrocarbon receptor (AhR), an in vitro assessment system for AhR activity was used in this study to search for flavonoids that attenuated dioxin toxicity through the intestinal epithelial monolayer. When AhR transformation in Hepa-1c1c7 cells was examined by southwestern ELISA, nine flavonoids among 34 kinds of flavonoids inhibited the transformation by more than one-half. When each flavonoid with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) was added to dioxin-responsive HepG2 cells, seven flavonoids significantly restrained the TCDD-induced transcriptional activity of the CYP1A1 promoter. Furthermore, those seven flavonoids that had permeated the Caco-2 cell monolayers demonstrated an inhibitory effect on both the AhR transformation and on the transcriptional activity of the CYP1A1 promoter. The expression level of the CYP1A1 mRNA and protein induced by TCDD was suppressed by flavone, galangin, and tangeretin. It is proposed from these results that some flavonoids have the ability to suppress dioxin-induced AhR activity after permeating the human intestinal epithelial cell monolayer.
AMER CHEMICAL SOC, 2006年11月, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 54 (23), 8891 - 8898, 英語[査読有り]
研究論文（学術雑誌）
Dioxins enter the body mainly through diet and cause the various toxicological effects by binding to the cytosolic aryl hydrocarbon receptor (AhR) followed by its transformation. In recent reports, it has been shown that certain natural compounds suppress AhR transformation in vitro. In this study, we demonstrated that ethanolic extract from molokhia, known as Egyptian spinach, showed the strongest suppressive effect on AhR transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in cell-free system using rat hepatic cytosol among 41 kinds of extracts from vegetables and fruits. The molokhia extract also suppressed TCDD-induced AhR transformation in mouse hepatoma Hepa-1c1c7 cells and in intestinal permeability system constructed with human colon adenocarcinoma Caco-2 cells and human hepatoma HepG2 cells. Moreover, oral administration of the molokhia extract (100 mg/kg body weight) decreased 3-methylcholanthrene-induced AhR transformation to the control level by inhibiting translocation of the AhR from cytosol into the nucleus in the liver of rats. The molokhia extract-administered rat liver showed a tolerance to TCDD-induced AhR transformation by ex vivo experiment. These results indicate that molokhia is an attractive food for isolation and identification of a natural antagonist for the AhR. (c) 2005 Elsevier Ltd. All rights reserved.
PERGAMON-ELSEVIER SCIENCE LTD, 2006年02月, FOOD AND CHEMICAL TOXICOLOGY, 44 (2), 250 - 260, 英語[査読有り]
研究論文（学術雑誌）
- Screening of indigenous plants from Japan for modulating effects on transformation of the aryl hydrocarbon receptor
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with which halogenated and polycyclic aromatic hydrocarbons such as dioxins and benzo[a]pyrene interact as ligands. Since such compounds cause various toxicological effects, including cancer, through the transformation of AhR, it is important to determine influence of modulating factors. It has been reported that certain plant components such as flavonoids and indoles can affect AhR transformation. In this study, to obtain clues to novel ligands of AhR, 191 species of indigenous plants were collected in Japan, and their 50% methanolic extracts (total 368 plant parts) were tested for modulating effects on AhR transformation in a cell-free system using a rat hepatic cytosolic fraction. Among tested extracts at a concentration of 1 mg dry weight of plant/mL, 174 of 368 extracts suppressed 1 nM 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD)-induced AhR transformation to 50% or less, while 9 extracts per se induced AhR transformation equivalent to more than 20% of that induced by 1 nM TCDD. Mallotus japonicus (Thunb.) Muell. (leaf) and Trichosanthes rostrata Kitamura (fruit and fruit skin) strongly suppressed 1 nM TCDD-induced AhR transformation, while Phellodendron amurense Ruprecht (seed) per se strongly induced AhR transformation. These results suggest that a large variety of plants in Japan contain various compounds modulating, mainly suppressing, AhR transformation.
Asian Pacific Organization for Cancer Prevention, 2006年, Asian Pacific Journal of Cancer Prevention, 7 (2), 208 - 220, 英語[査読有り]
研究論文（学術雑誌）
- 2006年, ITE Letters on Batteries, New Technologies & Medicine, 7(3), 292-295, 英語(+)-Catechin suppresses the inhibition of 3T3-L1 differentiation by 2,3,7,8-tetrachlorodibenzo-p-dioxin
[査読有り]
研究論文（学術雑誌）
- 2006年01月, Journal of Clinical Biochemistry and Nutrition, Vol. 39, No. 1, pp. 32-39, 英語A frequent drinking of green tea lowers the levels of endogenous oxidative stress in small intestines, erythrocytes and kidneys in rats
[査読有り]
研究論文（学術雑誌）
Suppressive effects of ethanolic extracts prepared from propolis group 12 and its main botanical origin (leaf bud of Bacchads dracunculifolia) on transformation of the aryl hydrocarbon receptor (AhR), the initial action of dioxin toxicity, were investigated. It was found that suppressive effects of propolis on AhR transformation were relatively higher than those of resins of its botanical origin in cell-free system and in Hepa-1c1c7 cells. When the composition of chemical ingredients was measured, propolis contained slightly higher amounts of flavonoid aglycones as compared with its botanical origin with the same characteristics. Moreover, antiradical activity, one of the typical biological activities of flavonoids, in propolis was also slightly higher than that in its botanical origin. These results indicate that not only propolis but also its botanical origin contains high amounts of flavonoid aglycones and that both of them are useful dietary sources for flavonoids with a potency to prevent dioxin toxicity.
AMER CHEMICAL SOC, 2005年12月, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 53 (26), 10306 - 10309, 英語[査読有り]
研究論文（学術雑誌）
- 2005年09月, ITE Letters on Batteries, New Technologies & Medicine, 6 4 372-377, 英語Suppressive effects of commercial beverages on TCDD-induced aryl hydrocarbon receptor transformation
[査読有り]
研究論文（学術雑誌）
- Black tea theaflavins suppress dioxin-induced transformation of the aryl hydrocarbon receptor
Dioxins cause various adverse effects through transformation of aryl hydrocarbon receptor (AhR). In this study, we investigated whether black tea extract and its components, theallavins, suppress AhR transformation in vitro. First, we confirmed that black tea extract strongly suppressed AhR transformation compared to green and oolong tea, although the catechin contents did not change significantly among the extracts. Then we isolated four theaflavins as active compounds from black tea leaves. They suppressed 1 nm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AhR transformation in a dose-dependent manner. The IC50 values of theaflavin, theaffavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate (Tfdg) were 4.5, 2.3, 2.2, and 0.7 mu m, respectively. The suppressive effect of Tfdg was observed not only by pre-treatment but also by post-treatment. This suggests that theaflavins inhibit the binding of TCDD to the AhR and also the binding of the transformed AhR to the specific DNA-binding site as putative mechanisms.
TAYLOR & FRANCIS LTD, 2005年05月, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 69 (5), 883 - 890, 英語[査読有り]
研究論文（学術雑誌）
- Anthocyans fail to suppress transformation of aryl hydrocarbon receptor induced by dioxin
Dioxins induce adverse effects through transformation of the cytosolic aryl hydrocarbon receptor (AhR). Our previous study found that flavones and flavonols at dietary levels suppress AhR transformation. In the present study, we investigated whether 20 anthocyans dissolved in trifluoroacetic acid (TFA)-MeOH suppressed AhR transformation in a cell-free system and in Hepa-1c1c7 cells. Although four compounds at 50 mu m suppressed 0.1 nm 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AhR transformation and their effects were dose-dependent in the cell-free system, they were ineffective at 0.5 mu m, which is close to physiological concentration. Moreover, no anthocyan at 50 mu m tested here suppressed 0.1 nm TCDD-induced AhR transformation in Hepa-1c1c7 cells. We also confirmed that protocatechuic acid and related compounds, which are possible metabolites of anthocyans, did not affect the transformation in the cell-free system. It is concluded that anthocyans are not suitable candidates for protection from dioxin toxicity.
TAYLOR & FRANCIS LTD, 2005年05月, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 69 (5), 896 - 903, 英語[査読有り]
研究論文（学術雑誌）
- 2005年, Proceedings of 2004 International Conference on O-CHA(tea) Culture and Science, 594-595, 英語Tea has the potential to reduce the dioxin risk
研究論文（国際会議プロシーディングス）
- 2005年, Proceedings of 2004 International Conference on O-CHA(tea) Culture and Science, 513-514, 英語Intake of green tea increases antioxidative potency in rats
研究論文（国際会議プロシーディングス）
Environmental contaminants such as dioxins enter the body mainly through diet and cause various toxicities through transformation of the aryl hydrocarbon receptor (AhR). We previously reported that certain natural flavonoids at the dietary level suppress the AhR transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study, we identified lutein and chlorophyll a and b from green tea leaves as the novel antagonists for AhR. These active compounds suppressed AhR transformation dose-dependently with the 50% inhibitory concentration (IC50) values against 0.1 nM TCDD-induced AhR transformation at 3.2, 5.0, and 5.9 muM, respectively. (-)-Epigallocatechin gallate, which is the most abundant flavonoid in green tea leaves, also showed stronger suppressive effects than did other major tea components, with the IC50 value of 1.7 muM. Thus, these pigments of green tea leaves have the potential to protect from dioxin toxicity through the suppression of AhR transformation.
AMER CHEMICAL SOC, 2004年05月, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 52 (9), 2499 - 2506, 英語[査読有り]
研究論文（学術雑誌）
- Suppression of dioxin mediated aryl hydrocarbon receptor transformation by ethanolic extracts of propolis
Present study demonstrated that the ethanolic extracts of propolis containing higher concentrations of flavonoids suppressed 2,3,7,8-tetrachlorodibenzo-p-di-oxin (TCDD)-induced aryl hydrocarbon receptor transformation in a dose-dependent manner. The IC50 values of propolis group 3 and group 12 were 1.2 and 3.6 mug/ ml, respectively, indicating that propolis showed stronger antagonistic effects as compared with vegetable extracts.
TAYLOR & FRANCIS LTD, 2004年04月, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 68 (4), 935 - 938, 英語研究論文（学術雑誌）
Halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), produce a wide variety of biological and toxic effects mainly through the aryl hydrocarbon receptor (AhR)-dependent mechanism. After the binding of HAHs, the AhR subsequently transforms its form in order to interact with a specific DNA sequence, the dioxin responsive element (DRE). Thus, detection of the transformed AhR is a target for estimation of the biological and toxic potency of ligands. In this study, we have developed a simple method for quantitative assessment of the transformation state of AhR based on an enzyme-linked immunosorbent assay (ELISA) combined with southwestern chemistry technique (SW-ELISA) that detects the complex of transformed AhR:fluorescein isotbiocyanate (FITC)-labeled DRE probe. SW-ELISA has shown the response to HAHs including TCDD and other known agonists in a dose-dependent manner. In the case of TCDD, SW-ELISA has revealed a minimum detection limit (MDL) of 2 pM (0.026 pg/assay), a median effective concentration (EC50) value of 0.125 nM (1.6 pg/assay), and a maximum response at 10 nM (129 pg/assay). Furthermore, SW-ELISA provides the confirmation that flavonoids, the potent antagonists for AhR as reported previously, show the inhibitory effects on TCDD-induced AhR transformation. These results indicate that SW-ELISA is a new and straightforward method for the detection of AhR transformation and will be useful in screening of agonists or antagonists for AhR. (C) 2004 Elsevier B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2004年04月, JOURNAL OF IMMUNOLOGICAL METHODS, 287 (1-2), 187 - 201, 英語研究論文（学術雑誌）
- Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver
Induction of xenobiotics metabolizing enzymes is related to the formation and chemoprevention of cancer. Since cytochrome P450s (CYPs) including CYP1A subfamily metabolize certain pro-carcinogens to their ultimate forms, downregulation of CYP1As by food factors leads to the prevention of cancer. Mushroom polysaccharides, especially beta-glucans such as lentinan from Lentinus edodes, possess the anti-tumor and immunomodulating activities through the cytokine production from immunocytes. Recent our studies have demonstrated that lentinan suppresses hepatic CYP1As expression in the both constitutive and inducible levels through the production of tumor necrosis factor-a and an increase in the DNA-binding activity of nuclear factor-kappaB. This paper discusses on the effective lentinan dosage and route of administration for suppression of CYP1As.
WILEY-BLACKWELL, 2004年, BIOFACTORS, 21 (1-4), 407 - 409, 英語研究論文（学術雑誌）
- Black tea extract suppresses transformation of aryl hydrocarbon receptor induced by dioxin
Dioxins cause various adverse effects through binding to an aryl hydrocarbon receptor (AhR) and transformation of the receptor. In this study, we investigated whether black tea extract suppresses AhR transformation. Dried black tea leaves were extracted with 75% ethanol, and the extract was pretreated to the rat liver cytosol fraction 10 min prior to addition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Transformed AhR was detected by electrophoretic gel mobility shift assay. Black tea extract suppressed AhR transformation in a dose-dependent manner, and the IC(50) value against 1 nM TCDD-induced AhR transformation was 8.9 mug/ml. The result suggests that intake of black tea has a potential to suppress the AhR transformation, leading protection from dioxin toxicity.
WILEY-BLACKWELL, 2004年, BIOFACTORS, 21 (1-4), 367 - 369, 英語[査読有り]
研究論文（学術雑誌）
- Anthocyan does not suppress transformation of aryl hydrocarbon receptor induced by dioxin
Dioxins cause a variety of toxic effects through transformation of a cytosolic aryl hydrocarbon receptor (AhR). We have previously demonstrated that certain natural flavones and flavonols at the dietary levels suppress AhR transformation. In this study, we investigated whether 5 anthocyanidins, 15 anthocyanins, and protocatechuic acid suppress AhR transformation in mouse hepatoma Hepa-1c1c7 cells. All the compounds tested here at 5 muM unexpectedly failed to suppress the transformation induced by 0.1 nM TCDD, indicating that anthocyan does not have a potential to prevent dioxin toxicity.
IOS PRESS, 2004年, BIOFACTORS, 21 (1-4), 371 - 373, 英語[査読有り]
研究論文（学術雑誌）
- Suppression of cytochrome P4501 a subfamily in mouse liver by oral intake of polysaccharides from mushrooms, Lentinus edodes and Agaricus blazei
Mushrooms have been consumed as flavorful and medicinal foods for millenniums. Mushroom polysaccharides possess antitumor activity through the stimulation of cytokine productions from immunocytes. On the other hand, lipopolysaccharide suppresses the expression of various hepatic cytochrome P450s (CYPs) through the production of cytokines such as tumor necrosis factor (TNF)-alpha. In this study, lentinan prepared from Lentinus edodes and polysaccharides from Agaricus blazei (ABPS) were intraperitoneally injected to female BALB/c mice, and the effects of these polysaccharides on the expression of CYPs were investigated in the liver. Both polysaccharides down-regulated the activity and level of constitutive and 3-methylcholanthrene-inducible CYP1A accompanied by the TNF-alpha production. When lentinan was orally administered to mice, down-regulation of the level and activity of CYP1A through the suppression of DNA binding activity of aryl hydrocarbon receptor also occurred. These results suggest that the mushroom polysaccharides such as lentinan and ABPS have an anti-carcinogenic activity, since the down-regulation of CYP1A is considered to prevent the metabolic activation of procarcinogens.
AMER CHEMICAL SOC, 2003年, FOOD FACTORS IN HEALTH PROMOTION AND DISEASE PREVENTION, 851, 235 - 248, 英語[査読有り]
研究論文（学術雑誌）
- N-Acetyl-L-cysteine suppresses constitutive expression of CD11a/LFA-1 protein in myeloid lineage
We investigated the possible involvement of redox regulation in constitutive expression of CD11a/LFA-1alpha, a leukocyte integrin alpha subunit, in myeloid cells using antioxidants. In unstimulated HL-60 cells, CD11a/LFA-1alpha was highly expressed, however, no expression of CD11b and CD11c proteins was detected. N-acetyl-L-cysteine (NAC) markedly down-regulated CD11a/LFA-1alpha expression in a dose-dependent manner. The down-regulated CD11a/LFA-alpha expression was gradually recovered when NAC was deprived 24 h after treatment. Pyrrolidine dithiocarbamate (PDTC) also suppressed the level of expression CD11a/LFA-1alpha protein, although the effect of PDTC was less potent than NAC. Both NAC and PDTC suppressed NF-kappaB binding activity to consensus DNA probe, and this result was correlated with a suppressive effect to CD11a/LFA-1alpha expression. Furthermore, NAC also down-regulated CD11a/LFA-1alpha expression in both U937 cells and peripheral blood monocytes. These results indicated that the constitutive CD11a/LFA-1alpha expression in the myeloid lineage is implicated in oxidative stress occurring spontaneously, suggesting that alteration of the intracellular redox state using antioxidants may be effective in the modulation of cell adhesion associated with extravasation in leukocytes, at least, in myeloid cells. (C) 2002 Elsevier Science Ltd. All rights reserved.
PERGAMON-ELSEVIER SCIENCE LTD, 2002年10月, Leukemia Research, 26 (10), 939 - 944, 英語[査読有り]
研究論文（学術雑誌）
- Up-regulation of CD13/aminopeptidase N induced by phorbol ester is involved in redox regulation and tumor necrosis factor alpha production in HL-60 cells
Here, we demonstrate the possible involvement of oxidative stress in altered CD13/aminopeptidase N (APN) expression during myeloid cell differentiation induced by TPA. In flow cytometrical analysis, CD13/APN protein was constitutively expressed in HL-60 cells. When the cells were treated with TPA, CD13/APN expression was up-regulated with increased intracellular peroxides and a morphological change into macrophage-like cells. This increase in CD13/APN expression was suppressed by treatment with N-acetylcysteine. Transfection of Mn-superoxide dismutase (MnSOD) gene to the cells also suppressed the up-regulated CD13/APN expression. Furthermore, a neutralizing antibody to TNFalpha partially blocked this up-regulation. These results indicate that the change in intracellular redox state could be involved in the up-regulation of CD13/APN expression during TPA-induced differentiation of HL-60 cells, suggesting that TNFalpha may serve as, at least, one of the signals stimulated by TPA.
SPRINGER/PLENUM PUBLISHERS, 2002年08月, INFLAMMATION, 26 (4), 175 - 181, 英語[査読有り]
研究論文（学術雑誌）
- Suppressive effect of polysaccharides from the edible and medicinal mushrooms, Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450s in mice
To investigate the effects of lentinan from Lentinas edodes and polysaccharides from Agaricus blazei (ABPS) on the expression of cytochrome P450s (CYPs), lentinan (10 mg/kg/day) or ABPS (200 mg/kg/day) was administered to female BALB/c mice four times every other day by intraperitoneal injection. Lentinan and ABPS suppressed both the constitutive and 3-methylcholanthrene-induced CYP1A expression and ethoxyresorufin-O-deethylation activity in the liver.
TAYLOR & FRANCIS LTD, 2002年07月, BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 66 (7), 1610 - 1614, 英語[査読有り]
研究論文（学術雑誌）
3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), a contaminant in our daily diet, induces apoptosis in cultured immunocytes. In this study, Trp-P-1 (1 mg/kg) was injected introperitoneally into male Wistar rats to investigate whether Trp-P-1 induces apoptosis in immune tissues in vivo. In the thymus, Trp-P-1 induced DNA fragmentation and morphological changes. Trp-P-1 also activated the initiator and executioner caspases, caspase-8 and -3, respectively, and activated caspase-3 in turn cleaved its intracellular substrate poly(ADP-ribose) polymerose 1 hr after injection. On the other hand, Trp-P-1 upregulated anti-apoptotic factors Bcl-2 and Bcl-XL and downregulated pro-apoptotic factor Bax in mitochondria 1 hr after injection, indicating that Trp-P-1 also stimulated anti-apoptotic signals. Trp-P-1 activated the serine-threonine protein kinase Akt, which is known to be an anti-apoptotic protein, and increased the DNA binding activities of apoptosis-associated transcription factors NF-κB and AP-1. In addition to the thymus, increases in the activities of these transcription factors were also observed in the spleen and in mononuclear cells from the blood. Therefore, Trp-P-1 activates both pro- and antiapoptotic signals in vivo in the immune system, particularly in the thymus, and the former signal overcomes the latter. © 2002 Wiley-Liss, Inc.
2002年, Environmental and Molecular Mutagenesis, 40 (3), 175 - 183, 英語[査読有り]
研究論文（学術雑誌）
- The heterocyclic amine, 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole induces apoptosis in cocultures of rat parenchymal and nonparenchymal liver cells
In this study, we investigated the mechanism of apoptosis by 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) in cocultures of parenchymal and nonparenchymal liver cells, since the liver consists of various cell types and they cooperatively respond to chemicals. It was found that cocultures were more susceptible to cell death by Trp-P-1 than culture of each cell type alone. In cocultures, Trp-P-1 induced DNA fragmentation accompanied by the activation of 18-kDa endonuclease. Trp-P-1 (30 muM) caused a rapid increase in Bid protein level in mitochondria and the leakage of cytochrome c from mitochondria into the cytosol 15 min after treatment. On the other hand, an increase in Bax protein and a decrease in Bcl-2 protein were detected in the mitochondrial fraction 2 h after treatment following the increases in p53 protein level and DNA binding activity of NF-kappaB. Caspase-8 was activated within 30 min followed by the activation of downstream caspases as measured using the corresponding peptide substrates. The activation of caspases was also confirmed by cleavage of caspase-3, poly(ADP-ribose)polymerase, and protein kinase C-a as analyzed by Western blotting. A peptide inhibitor of caspase-8 diminished DNA ladder formation and the activation of downstream caspases, but a caspase-9 inhibitor and pyrrolidinedithiocarbamate as an inhibitor of NF-kappaB showed only partial inhibition, suggesting that caspase-8 is the apical caspase in the cascade. These results led to the conclusion that Trp-P-1 mainly drives the caspase-8-mediated pathway that involves Bid, accompanied by a delay in the p53/NF-kappaB-mediated side pathway that involves Bax, Bcl-2, and caspase-9. (C) 2001 Academic Press.
ACADEMIC PRESS INC, 2001年11月, TOXICOLOGY AND APPLIED PHARMACOLOGY, 177 (1), 59 - 67, 英語[査読有り]
研究論文（学術雑誌）
- Flavones and flavonols at dietary levels inhibit a transformation of aryl hydrocarbon receptor induced by dioxin
Dioxins invade the body mainly through the diet, and produce toxicity through the transformation of aryl hydrocarbon receptor (AhR), An inhibitor of the transformation should therefore protect against the toxicity and ideally be part of the diet. We examined flavonoids ubiquitously expressed in plant foods as one of the best candidates, and found that the subclasses flavones and flavonols suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8-tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform AhR. The antagonistic IC50 values ranged from 0.14 to 10 mu M, close to the physiological levels in human. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
ELSEVIER SCIENCE BV, 2000年07月, FEBS LETTERS, 476 (3), 213 - 217, 英語[査読有り]
研究論文（学術雑誌）
MISC
- (公財)日本ビフィズス菌センター, 2019年04月, 腸内細菌学雑誌, 33 (2), 105 - 105, 日本語日本人潰瘍性大腸炎患者の腸内細菌叢における2種の酪酸産生遺伝子の定量
- 医学書院, 2015年11月, 公衆衛生, 79 (11), 753 - 757, 日本語食品トレーサビリティシステム
[招待有り]
記事・総説・解説・論説等（学術雑誌）
- 日本生物工学会, 2011年, 生物工学会誌, 89 (2), 71 - 71, 日本語生物工学会論文賞紹介記事「パン酵母β-グルカンのラットにおける脂質異常症予防効果 」(生物工学会誌, 87 (3),129－134, 2009掲載分)
[招待有り]
書評論文,書評,文献紹介等
- 日本生物工学会, 2010年, 日本生物工学会大会講演要旨集, 22, 97 - 97, 日本語3P-1159 キャピラリー電気泳動法を利用したタンパク質-食品因子間相互作用の解析(4b食品科学,食品工学,一般講演,醸造・食品工学,伝統の技と先端科学技術の融合)
- 日本生物工学会, 2009年, 日本生物工学会大会講演要旨集, 21, 258 - 258, 日本語3S10p03 アントラキノン類のアリール炭化水素受容体活性化抑制作用の構造活性相関について(構造活性相関研究の最新の動向,シンポジウム)
- KARGER, 2009年, ANNALS OF NUTRITION AND METABOLISM, 55, 278 - 279, 英語POLYPHENOLS PROMOTE GLUCOSE UPTAKE IN SKELETAL MUSCLE CELLS ACCOMPANIED BY THE TRANSLOCATION OF GLUCOSE TRANSPORTER 4 ON PLASMA MEMBRANE
研究発表ペーパー・要旨（国際会議）
- 2009年, 日本醸造教会誌, 104 (12), 939 - 943, 日本語パン酵母β-グルカンの整腸作用について
記事・総説・解説・論説等（学術雑誌）
Background: Halogenated aromatic hydrocarbons including dioxins and non-halogenated polycyclic aromatic hydrocarbons are ligands of an aryl hydrocarbon receptor (AhR) and stimulate its transformation. Exposure to these environmental contaminants occurs mainly through diet. Recent articles demonstrated that certain food factors regulate the AhR transformation and expression of downstream drug-metabolizing enzymes. Objective: To explain the actions of these food factors on the AhR transformation, as the mechanisms underlying are not fully understood. Methods: This review introduces recent articles that have demonstrated the molecular mechanisms by which food factors regulate the AhR transformation and downstream drug-metabolizing enzymes. Results/conclusion: The role of classical ligands including dioxins as agonists of the receptor is well documented. As to the food factors, they act as antagonists because they basically suppress the AhR transformation by different mechanisms. Moreover, the fate and metabolism of food factors are important to understand their mechanisms.
INFORMA HEALTHCARE, 2008年11月, EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 4 (11), 1429 - 1447, 英語[査読有り]
書評論文,書評,文献紹介等
- 日本工業出版, 2008年, 検査技術, 13(8),15-20 (8), 15 - 20, 日本語ダイオキシン類の生物学的超微量測定法
記事・総説・解説・論説等（学術雑誌）
- AMER CHEMICAL SOC, 2006年09月, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 232, 112 - 112, 英語Suppressive effects of flavonoids on activation of the aryl hydrocarbon receptor induced by dioxins
研究発表ペーパー・要旨（国際会議）
- (公社)日本栄養・食糧学会, 2006年04月, 日本栄養・食糧学会大会講演要旨集, 60回, 206 - 206, 日本語筋肉細胞における(-)-エピガロカテキンガレートによるグルコースの取り込み亢進作用機構について
- (公社)日本栄養・食糧学会, 2006年04月, 日本栄養・食糧学会大会講演要旨集, 60回, 235 - 235, 日本語芳香族炭化水素により誘導されるアリール炭化水素受容体の形質転換に対するカカオポリフェノールの抑制効果
- 日本生物工学会, 2004年, 生物工学会誌, 82(10) 477-480 (10), 477 - 480, 日本語カテキンのダイオキシン毒性予防作用
その他
書籍等出版物
- 共著, 朝倉書店, 2017年, 日本語環境汚染物質除去作用: 「茶の事典」
学術書
- 共著, Academic Press, 2013年, 英語Modulation of drug-metabolizing enzymes and transporters by polyphenols as one of the anti-carcinogenic effects. In "Polyphenols in Human Health and Diseases": Vol. 2. Eds by Ronald Ross Watson, Victor R. Preedy, and Sherma Zibadi. Chapter 86, pp. 1127-11
学術書
- 共著, American Chemical Society, 2011年, 英語Suppressive Effects of Flavonoids on Activation of the Aryl Hydrocarbon Receptor Induced by Dioxins, in “Functional Food and Health”, Chapter 31, Eds. by Takayuki Shibamoto, Kazuki Kanazawa, Fereidoon Shahidi, and Chi-Tang Ho., ACS symposium series No.993
学術書
- 共著, シーエムシ－出版, 2009年, 日本語熱中性子放射化分析による定量分析、「メタルバイオテクノロジーによる環境保全と資源回収 ～新元素戦略の新しいキーテクノロジー～」、吉田和哉名誉監修・植田充美、池道彦監修、pp. 263-270.
学術書
- 共著, シーエムシー出版, 2009年, 日本語メタルバイオテクノロジーによる環境保全と資源回収 ～新元素戦略の新しいキーテクノロジー～
学術書
- 共著, American Chemical Society, 2008年, 英語Suppressive effects of flavonoids on activation of the aryl hydrocarbon receptor induced by dioxins. In: Functional Food and Health, T. Shibamoto, K. Kanazawa, F. Shahidi, and C.-T. Ho, eds., pp. 369-374.
学術書
- 共著, シー・エム・シー出版, 2006年, 日本語「芳香族炭化水素の毒性発現抑制作用への可能性」茶の効能と応用開発，伊勢村護監修，pp. 316-326．
学術書
- 単著, 博士論文, 2005年, 英語Studies on Suppression of the Dioxin Toxicity by Food Factors
学術書
- その他, American Chemical Society, 2003年, 英語Suppression of Cytochrome P4501A Subfamily in Mouse Liver by Oral Intake of Polysaccharides from Mushrooms, Lentinus edodes and Agaricus blazei.(Chapter 21, 235-248), In "Food Factors in Health Promotion andDisease Prevention"
学術書
- 共著, American Chemical Society, 2003年, 英語Suppression of Cytochrome P4501A Subfamily in Mouse Liver by Oral Intake of Polysaccharides from Mushrooms, Lentinus edodes and Agaricus blazei.(Chapter 21, 235-248)
学術書
- その他, American Chemical Society, 2003年, 英語Green Tea Extracts Prevent the Dioxin Toxicity through the Suppression of Transformation of the Aryl Hydroarbon Receptor.(Chapter 11, pp.119-127), In "Food Factors in Health Promotion andDisease Prevention"
学術書
- 共著, In "Food Factors in Health Promotion and Disease Prevention", 2003年, 英語Green Tea Extracts Prevent the Dioxin Toxicity through the Suppression of Transformation of the Aryl Hydroarbon Receptor.(Chapter 11, pp.119-127)
学術書
講演・口頭発表等
- 第70回日本生物工学会大会, 2018年09月, 日本語, 関西大学 千里山キャンパス, 国内会議腸内細菌Bacteroides thetaiotaomicronによる食物繊維の資化性に関する研究
ポスター発表
- 第70回日本生物工学会大会, 2018年09月, 日本語, 関西大学 千里山キャンパス, 国内会議in vitro培養系ヒト腸内細菌叢モデル（KUHIMM） を用いた難消化性食物繊維の影響評価
ポスター発表
- 第70回日本生物工学会大会, 2018年09月, 日本語, 関西大学 千里山キャンパス, 国内会議In vitro培養系ヒト腸内細菌叢モデルによる潰瘍性大腸炎患者の代謝プロファイル異常の検出
ポスター発表
- The 6th International Conference on Food Factors (ICoFF 2015), 2015年11月, 英語, COEX, Seoul, Republic of Korea, 国際会議Lactobacillus plantarum 22A-3 enhances anti-oxidant activity of (-)-epigallocatechin-3-gallate in C57BL/6J mice
ポスター発表
- 2015年度 日本乳酸菌学会泊まり込みセミナー, 2015年05月, 日本語, サンライズ淡路, 国内会議ヒト腸管培養モデルを用いたイヌリン型フルクタンの有益 効果の検証
口頭発表（一般）
- The 33rd International Symposium on Halogenated Persistent Organic Pollutants and POPs (DIOXIN2013), 2013年, 英語, Daegu, Korea, 国際会議Inhibitory effect of cardamonin on transformation of aryl hydrocarbon receptor
ポスター発表
- 第59回日本食品科学工学会, 2012年, 日本語, 札幌, 国内会議蛍光分析法を利用したアシル化カテキンと血清アルブミンの相互作用の検討
口頭発表（一般）
- 第66回日本栄養・食糧学会大会, 2012年, 日本語, 仙台, 国内会議マウスおよびラットにおける黒大豆種皮抽出物の蛍光毒性評価
口頭発表（一般）
- 第17回日本フードファクター学会学術集会・第9回日本カテキン学会総会合同大会, 2012年, 日本語, 静岡, 国内会議カルコン類によるアリール炭化水素受容体の活性化抑制効果について
口頭発表（一般）
- The 32nd International Symposium on Halogenated Persistent Organic Pollutants and POPs (DIOXIN2012), 2012年, 英語, ケアンズ, 国際会議Induction of the multidrug-resistant Mdr1b mediatedby aryl hydrocarbon receptor in mouse hepatoma Hepa-1c1c7 cells
ポスター発表
- The 32nd International Symposium on Halogenated Persistent Organic Pollutants and POPs (DIOXIN2012), 2012年, 英語, ケアンズ, 国際会議Application of a southwestern-chemistry based ELISA to evaluation of dioxins in the farm products
ポスター発表
- 2012年度日本農芸化学会関西支部大会(第476回講演会), 2012年, 日本語, 亀岡, 国内会議3-メチルコラントレンによるアリール炭化水素受容体を介した多剤耐性遺伝子mdr1bの転写調節
口頭発表（一般）
- 第20回環境化学討論会, 2011年07月, 日本語, 日本環境化学会, 熊本, 国内会議医薬品類と水系フミン物質の吸着
ポスター発表
- 2011 International Conference on Food Factors (ICoFF2011), 2011年, 英語, 国際会議Cardamonin stimulates glucose uptake through translocation of glucose transporter-4 in L6 miotubes
ポスター発表
- 日本農芸化学会2010年度大会, 2010年, 日本語, 国内会議明日葉カルコン4-hydroxyderricinおよびxanthoangelolの糖取り込み促進作用とその分子機序の検討
口頭発表（一般）
- 京都大学原子炉利用者講演会, 2010年, 日本語, 国内会議食品中の機能成分の体内金属動態に対する作用
口頭発表（一般）
- 日本農芸化学会2010年度大会, 2010年, 日本語, 国内会議フラボノイドの体内動態と抗酸化能評価
口頭発表（一般）
- 日本農芸化学会2010年度大会, 2010年, 日本語, 国内会議グリコーゲンの消化酵素による分解性
口頭発表（一般）
- 第62回日本生物工学会, 2010年, 日本語, 国内会議キャピラリー電気泳動法を利用したタンパク質・食品因子間相互作用の解析
口頭発表（一般）
- 日本農芸化学会2010年度大会, 2010年, 日本語, 国内会議キャピラリー電気泳動法を用いたタンパク質と食品因子との相互作用の解析
口頭発表（一般）
- PACIFICHEM2010(環太平洋国際化学会議), 2010年, 英語, 国内会議4-Hydroxyderricin and xanthoangelol stimulate glucose uptake in skeletal muscle cells via inducing GLUT4 translocation
ポスター発表
- 日本腐植物質学会第25回講演会, 2009年11月, 日本語, 日本腐植物質学会, 兵庫, 国内会議腐植物質に対する医薬品類の収着
口頭発表（一般）
- 日本農芸化学会2009年度大会, 2009年, 日本語, 国内会議緑茶投与がラット体毛の重金属量に及ぼす影響
口頭発表（一般）
- 第14回日本フードファクター学会, 2009年, 日本語, 国内会議明日葉カルコン4-hydroxyderricinおよびxanthoangelolの血糖値調節作用
ポスター発表
- 2009年日本農芸化学会関西・西日本合同支部大会, 2009年, 日本語, 国内会議茶の白色脂肪蓄積抑制作用におけるカフェインとカテキンの寄与について
口頭発表（一般）
- 日本食品学工学会第56回大会, 2009年, 日本語, 国内会議細胞内糖取り込みを誘導するポリフェノールの探索とその作用機構の解明
口頭発表（一般）
- 第63回日本栄養・食糧学会大会, 2009年, 日本語, 国内会議高脂肪食摂取マウスにおける酵素合成グリコーゲンの脂質代謝に対する影響
口頭発表（一般）
- 第14回日本フードファクター学会, 2009年, 日本語, 国内会議紅茶糖尿病予防および改善効果について
ポスター発表
- 日本食品学工学会第56回大会, 2009年, 日本語, 国内会議筋肉組織における糖輸送担体GLUT4の細胞膜移行に及ぼすプロポリス抽出物の影響について
口頭発表（一般）
- 第14回日本フードファクター学会, 2009年, 日本語, 国内会議筋肉細胞におけるアシル化カテキンによるGLUT4膜移行促進効果とその作用機構について
ポスター発表
- 日本農芸化学会2009年度大会, 2009年, 日本語, 国内会議ヨモギ抽出物によるGLUT4膜移行促進作用機構の解明
口頭発表（一般）
- 第24回日本香辛料研究会, 2009年, 日本語, 国内会議ショウガ科植物成分カルダモニンおよびアルピネチンの筋細胞におけるGLUT4依存的な糖取込促進作用
口頭発表（一般）
- 第61回日本生物工学会, 2009年, 日本語, 国内会議アントラキノン類のアリール炭化水素受容体活性化抑制作用の構造活性相関について
ポスター発表
- The 5th International Workshop on Anthocyanins, 2009年, 英語, 国際会議Safety assessment of extract of black soybean seed coat: Acute and chronic toxicity studies
ポスター発表
- The 4th International Conference on Polyphenols and Health, 2009年, 英語, 国際会議Preventive effects of black soybean seed coat extract on obesity and hyperglycemia in high-fat diet-fed mice
ポスター発表
- 19th International Congress of Nutrition, 2009年, 英語, 国際会議Polyphenols promote glucose uptake in skeletal muscle cells accompanied by the translocation of glucose transporter 4 on plasma membrane
ポスター発表
- 日本農芸化学会2009年度大会, 2009年, 日本語, 国内会議L6筋管細胞におけるアシルカテキンによるインスリン応答性糖輸送担体(GLUT4)の細胞膜移行促進効果
口頭発表（一般）
- The 4th International Conference on Polyphenols and Health, 2009年, 英語, 国際会議Epigallocatechin-3-gallate regulate glucose metabolism in skeletal muscle cells
ポスター発表
- The 4th International Conference on Polyphenols and Health, 2009年, 英語, 国際会議4-Hydroxyderricin and xanthoangelol, prenylated chalcones from Ashitaba (Angelica keiskei), stimulate glucose uptake in skeletal muscle cells via inducing GLUT4 translocation
ポスター発表
- 2005 International chemical congress of pacific basin societies (PACIFICHEM 2005) December 15th-20th, Programp.4TECH, #162, Abstract is available on CD., 2005年12月, 英語, 未記入, Honolulu, Hawaii, 国際会議Prevention of dioxin toxicity by food factores
口頭発表（一般）
- 2005年度日本農芸化学会大会講演要旨集, 2005年03月, 日本語, 日本農芸化学会, 札幌, 国内会議茶の飲用はアリール炭化水素受容体の活性化を抑制する
口頭発表（一般）
- 日本動物細胞工学会2005年度大会 講演要旨集p.64, 2005年, 日本語, 日本動物細胞工学会, 東京, 国内会議腸管上皮を透過しダイオキシンの毒性発現を抑制しうるフラボノイド類の検索及び解析
口頭発表（一般）
- 日本動物細胞工学会2005年度大会 講演要旨集p.58, 2005年, 日本語, 日本動物細胞工学会, 東京, 国内会議モロヘイヤはアリール炭化水素受容体の形質転換を抑制する
口頭発表（一般）
- 日本農芸化学会2005年度関西・中四国・西日本支部合同大会 講演要旨集p.75, 2005年, 日本語, 日本農芸化学会, 大阪, 国内会議フラボノイド類とアリール炭化水素受容体との相互作用について
口頭発表（一般）
- 日本農芸化学会2005年度大会 大会講演要旨集p.274, 2005年, 日本語, 日本農芸化学会, 札幌, 国内会議ダイオキシン類の毒性発現を抑制するフラボノイド類の検索及び解析
口頭発表（一般）
- 日本農芸化学会2005年度大会 大会講演要旨集p.285, 2005年, 日本語, 日本農芸化学会, 札幌, 国内会議カテキンがインスリン応答性糖輸送活性に及ぼす影響
口頭発表（一般）
- 第10回日本フードファクター学会（JSoFF） 講演要旨集p.61, 2005年, 日本語, 日本フードファクター学会, 岡山, 国内会議インジゴイドがアリール炭化水素受容体の形質転換に及ぼす影響について
口頭発表（一般）
- 第28回日本分子生物学会年会 講演要旨集p.479, 2005年, 日本語, 日本分子生物学会, 博多, 国内会議アリール炭化水素受容体複合体に対するフラボノイド類の作用機序の解明
ポスター発表
- 日本農芸化学会2005年度大会 大会講演要旨集p.118, 2005年, 日本語, 日本農芸化学会, 札幌, 国内会議アリール炭化水素受容体の形質転換に影響をおよぼす植物の検索
口頭発表（一般）
- 日本農芸化学会2005年度大会 大会講演要旨集p.99, 2005年, 日本語, 日本農芸化学会, 札幌, 国内会議(-)-エピガロカテキンガレートとアリール炭化水素受容体との相互作用について
口頭発表（一般）
- 第3回ポリフェノール研究会（組織保存液開発プレベンチャーグループ研究会）, 2004年, 日本語, ポリフェノール研究会, 未記入, 国内会議茶カテキンと受容体との相互作用について
口頭発表（一般）
- 近畿地域アグリビジネス創出フェア, 2004年, 日本語, 未記入, 未記入, 国内会議神戸大学農学部生物機能化学科生物機能開発化学教育研究分野
口頭発表（一般）
- 2004年度日本農芸化学会本大会, 2004年, 日本語, 日本農芸化学会, 未記入, 国内会議プロポリスはアリール炭化水素受容体の活性化を抑制する
口頭発表（一般）
- 2004年度日本農芸化学会大会, 2004年, 日本語, 日本農芸化学会, 広島, 国内会議ブラジル産プロポリスはアリール炭化水素受容体の活性化を抑制する
口頭発表（一般）
- 第58回日本栄養・食料学会, 2004年, 日本語, 日本栄養・食料学会, 仙台, 国内会議パン酵母β-グルカン（BBG)のコレステロール吸収阻害効果について
口頭発表（一般）
- 2004年度日本農芸化学会本大会, 2004年, 日本語, 日本農芸化学会, 未記入, 国内会議ダイオキシン類のリスク評価のための新規測定法の構築
口頭発表（一般）
- 2004年度日本農芸化学会大会, 2004年, 日本語, 日本農芸化学会, 広島, 国内会議ダイオキシン類のリスク評価のための新規測定法の構築
口頭発表（一般）
- 2004年度日本農芸化学会大会, 2004年, 日本語, 日本農芸化学会, 広島, 国内会議アントシアンはアリール炭化水素受容体の活性化を抑制しない
口頭発表（一般）
- International Conference of O-CHA(tea) Culture and Science., 2004年, 英語, 未記入, 未記入, 国際会議Tea has the potential to reduce the dioxin risk.
口頭発表（一般）
- 2004 International Conference On O-CHA(tea) Culture And Science, 2004年, 英語, 未記入, 未記入, 国際会議Tea has the potential to reduce the dioxin risk.
口頭発表（一般）
- The Institute of Food Techcologists 2004 Annual Meeting., 2004年, 英語, 未記入, 未記入, 国際会議Suppression of dioxin mediated aryl hydrocarbon receptor transformation by ethanolic extracts of proplis and its main botanical origin.
口頭発表（一般）
- International Conference of O-CHA(tea) Culture and Science., 2004年, 英語, 未記入, 未記入, 国際会議Intake of green tea increases antioxidative potency in rats.
口頭発表（一般）
- 2004 International Conference On O-CHA(tea) Culture And Science, 2004年, 英語, 未記入, 未記入, 国際会議Intake of green tea increases antioxidative potency in rats.
口頭発表（一般）
- 日本食品科学工学会第50回大会講演要旨集, 2003年09月, 日本語, 日本食品科学工学会, 東京農業大学, 国内会議野菜および果物抽出物によるダイオキシン毒性の抑制効果
口頭発表（一般）
- 日本癌学会第62回総会総会記事, 2003年09月, 日本語, 日本癌学会, 名古屋国際会議場, 国内会議肝癌周囲硬変部におけるendoglin/CD105 発現の免疫組織化学的解析
口頭発表（一般）
- 2003年度日本農芸化学会本大会講演要旨集, 2003年, 日本語, 日本農芸化学会, 未記入, 国内会議野菜抽出物によるアリル炭化水素受容体形質転換抑制能について
口頭発表（一般）
- 2003年度日本農芸化学会本大会講演要旨集, 2003年, 日本語, 日本農芸化学会, 未記入, 国内会議フラボノイドとアリル炭化水素受容体との相互作用について
口頭発表（一般）
- 2003年度日本農芸化学会本大会講演要旨集, 2003年, 日本語, 日本農芸化学会, 未記入, 国内会議アリル炭化水素受容体を形質転換する食品因子とダイオキシンの作用との比較
口頭発表（一般）
- 第62回日本癌学会総会, 2003年, 日本語, 日本癌学会, 名古屋国際会議場, 国内会議アリール炭化水素受容体の活性化を測定するELISA の構築とこれを用いた食品成分のダイオキシン毒性抑制効果の評価
口頭発表（一般）
所属学協会
共同研究・競争的資金等の研究課題
- 学術研究助成基金助成金／基盤研究(C), 2018年04月 - 2021年03月, 研究代表者
競争的資金
- 科学研究費補助金／基盤研究(B), 2017年04月 - 2021年03月
競争的資金
- 学術研究助成基金助成金／若手研究(B), 2013年04月 - 2016年03月, 研究代表者
競争的資金
- 科学研究費補助金／若手研究(B), 2007年, 研究代表者
競争的資金