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Accumulation and Metabolism of Antioxidative Flavonoids on Oxidative Stress-Targeted Organs and Expression Mechanism of Their Activity

Research Project

Project/Area Number 16380089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionUniversity of Tokushima

Principal Investigator

TERAO Junji  University of Tokushima, Institute of Health Biosciences Graduate School, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (60093275)

Co-Investigator(Kenkyū-buntansha) MUROTA Kaeko  University of Tokushima, Assistant Professor, 大学院ヘルスバイオサイエンス研究部, 助教 (40294681)
KAWAI Yoshichika  University of Tokushima, Assistant Professor, 大学院ヘルスバイオサイエンス研究部, 助教 (50380027)
BANDO Noriko  University of Tokushima, Research Associate, 大学院ヘルスバイオサイエンス研究部, 教務員 (40116851)
AZUMA Keiko  National Institute for Vegetable and Tea Science, NAFRO Research Head, 野菜茶業研究所, ユニット長 (10355604)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥9,700,000 (Direct Cost: ¥9,700,000)
Keywordsflavonoid / oxidative stress / antioxidant / life style-related disease / blood aorta / high cholesterol / glucuronic acid conjugation / quercetin / 動脈硬化 / 内皮細胞 / マクロファージ / 潰瘍性大腸炎
Research Abstract

Numerous in vitro studies have revealed that dietary flavonoids possess diverse biochemical functions related to anti-atherosclerotic effect. Their antioxidant activity should, at least partly, underlies such a wide variety of functions. However, bioavailability of flavonoids has been questioned for long years, as their intestinal absorption seems to be hardly achieved. Furthermore, dietary flavonoids are mostly converted into inactive glucuronide and/or sulfate conjugates before reaching to the target organs. Thus, their inactive metabolites seem to circulate in the body at quite low concentration. Nevertheless, several biological activities of their metabolites were recently reported as similarly to their aglycones. We aimed to clarify the accumulation and metabolism of flavonoids in the target site for exerting their biological effect. Quercetin was selected as a representative of dietary flavonoids from vegetables and quercetin-3-0-D-glucuronide (Q3GA) was synthesized as a typical quercetin metabolite found in circulation. We discovered that quercetin metabolites accumulate in atherosclerotic aorta exclusively. This phenomenon implies that quercetin metabolites are incorporated into the atherosclerotic region and act as complementary antioxidants, when oxidative stress is loaded in the vascular system. This hypothesis is supported by the results that Q3GA was incorporated into macrophage cells and present as Q3GA, quercetin aglycone and its methylated form and that their distribution was modified by stimulating the cells with LPS. This modification is likely to be helpful in increasing biological activity of dietary quercetin. We found that these metabolites circulating in the human blood stream were mostly localized in plasma albumin fraction, indicating that plasma albumin is a carrier for translocation of quercetin metabolites to vascular target.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2007 2006 2005 Other

All Journal Article (18 results) Book (4 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Lowering effects of onion intake on oxidative stress biomarkers in streptozocin-induced diabetic rats2007

    • Author(s)
      Keiko Azuma
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition 40・2

      Pages: 131-140

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antioxidant capacity of albumin-bound quercetin metabolites after onion consumption in human2007

    • Author(s)
      Kaeko Murota
    • Journal Title

      Journal of Medical Investigation 54(In press)

    • NAID

      130004822563

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 機能性ポリフェノール2007

    • Author(s)
      寺尾純二
    • Journal Title

      化学と生物 44・10

      Pages: 688-698

    • NAID

      10018252558

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lowering effects of onion intake on oxidative stress biomarkers in streptozocin-nduced diabetic rats2007

    • Author(s)
      K.Azuma
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition 40, 2

      Pages: 131-140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Antioxidant capacity of albumin-bound quercetin metabolites after onion consumption in human2007

    • Author(s)
      K.Murota
    • Journal Title

      Journal of Medical Investigation 54(in press)

    • NAID

      130004822563

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lowering effects of onion intake on oxidative stress biomarkers in streptozocin-induced diabetic rats2007

    • Author(s)
      Keiko Azuma
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition 40(2)

      Pages: 131-140

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent ROS formation in PC-12 cells.2006

    • Author(s)
      Mutsuko Shirai
    • Journal Title

      Free Radical Research 40

      Pages: 1047-1053

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 野菜フラボノイドの生体利用性と抗酸化活性2006

    • Author(s)
      東 敬子
    • Journal Title

      ビタミン 54/8

    • NAID

      110004793369

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-ependent ROS formation in PC-12 cells2006

    • Author(s)
      M.Shirai
    • Journal Title

      Free radical Research 40

      Pages: 1047-1053

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent ROS formation in PC-12 cells2006

    • Author(s)
      Mutsuko Shirai
    • Journal Title

      Free Radical Research 40

      Pages: 1047-1053

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit2005

    • Author(s)
      Chiemi Kamada
    • Journal Title

      Free Radical Research 39・2

      Pages: 185-194

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro biological properties of flavonoid conjugates found in vivo2005

    • Author(s)
      G.Williamson
    • Journal Title

      Free Radical Research 39・5

      Pages: 457-469

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ケルセチン配糖体の吸収代謝と活性発現機構2005

    • Author(s)
      寺尾純二
    • Journal Title

      ビタミン 75・1

      Pages: 3-11

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit2005

    • Author(s)
      C.Kamada
    • Journal Title

      Free Radical Research 39,2

      Pages: 185-194

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vitro biological properties of flavonoid conjugates found in vivo2005

    • Author(s)
      C.Williamson
    • Journal Title

      Free Radical Research 39, 5

      Pages: 457-469

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high chotestero-fed rabbit2005

    • Author(s)
      C.Kamada, E.L.daSilva, M.Ohnishi-Kameyama, J-H.Moon, J.Terao
    • Journal Title

      FREE RADICAL RESEARCH 39(2)

      Pages: 185-194

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vitro biological properties of flavonoid conjugates found in vivo2005

    • Author(s)
      G.Williamson, D.Barron, K.Shimoi, J.Terao
    • Journal Title

      FREE RADICAL RESEARCH (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ケルセチン配糖体の吸収代謝と活性発現機構2005

    • Author(s)
      寺尾 純二
    • Journal Title

      ビタミン 75巻1号

      Pages: 3-11

    • Related Report
      2004 Annual Research Report
  • [Book] 食品成分のはたらき 8章1 フラボノイドの吸収代謝と抗酸化作用の制御2006

    • Author(s)
      寺尾純二
    • Total Pages
      12
    • Publisher
      朝倉書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] ビタミン(総合論文)野菜フラボノイドの生体利用性と抗酸化活性2006

    • Author(s)
      東 敬子
    • Total Pages
      8
    • Publisher
      日本ビタミン学会
    • Related Report
      2006 Annual Research Report
  • [Book] 化学と生物「セミナー室」機能性ポリフェノール2006

    • Author(s)
      寺尾純二
    • Total Pages
      11
    • Publisher
      日本農芸化学会
    • Related Report
      2006 Annual Research Report
  • [Book] 食品成分のはたらき 8章1フラボノイドの吸収代謝と抗酸化作用の制御(山田耕路(編者))2005

    • Author(s)
      寺尾純二
    • Publisher
      朝倉書店
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗ケルセチンモノクローナル抗体、その産生細胞、ケルセチンの検出方法および検出試薬2005

    • Inventor(s)
      河合 慶親
    • Industrial Property Rights Holder
      河合 慶親
    • Industrial Property Number
      2005-298972
    • Filing Date
      2005-10-13
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗ケルセチンモノクローナル抗体、その産生細胞、ケルセチンの検出方法および検出試薬

    • Inventor(s)
      河合慶親
    • Industrial Property Rights Holder
      河合慶親
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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