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Drug-food interaction on transporters

Research Project

Project/Area Number 16H05111
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical pharmacy
Research InstitutionKanazawa University

Principal Investigator

TAMAI IKUMI  金沢大学, 薬学系, 教授 (20155237)

Co-Investigator(Kenkyū-buntansha) 若山 友彦  熊本大学, 大学院生命科学研究部(医), 教授 (70305100)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsトランスポーター / マイクロRNA / 食品ナノ粒子 / 栄養素 / 食品高分子 / 薬物動態 / 食品 / 発現変動 / カテキン / 消化管吸収 / 相互作用 / 消化管機能 / ナノ粒子 / 薬食相互作用 / 消化管 / 食品成分 / 薬学 / 輸送体 / BCRP / OATP2B1 / 毒性 / 嗜好飲料
Outline of Final Research Achievements

Novel mechanism of food effect on human intestinal function was studied by focusing on microRNA included in food abundantly. By in vitro experiments, apple derived-nanoparticle (APNP) decreased mRNA and protein expression of intestinal transporters. 3’-UTR of transporter gene interacted with APNP. Furthermore, APNP included variable apple-derived microRNA, involvement of microRNA in this down regulation was suggested. Data-base analysis demonstrated that apple microRNA interact with the specific transporter gene. The suggested microRNA downregulated expression of the transporter gene and protein. Accordingly, since microRNA is a large molecule, it was clearly shown that food-derived large molecules such as microRNA directly affect intestinal function through nanoparticle of food, The conclusion also provides new concept of nutrients that food-derived large molecules are directly functional to affect human health.

Academic Significance and Societal Importance of the Research Achievements

食品の生体への作用は、従来は食品中の低分子(ビタミンなど)あるいは高分子であってもその代謝である低分子(アミノ酸など)が引き起こし、食品高分子は直接生体には作用しないものとされてきた。これに対し本成果は全く新しく、食品由来ナノ粒子を考慮することでマイクロRNAなどの食品含有高分子が直接的に栄養素としてヒトに働く可能性を示した。マイクロRNA以外の高分子が粒子には含まれるため、これまでの栄養学的な考えを変える必要を示すものとなった。さらに、食品による薬物作用変動機構として従来の低分子のみならず高分子作用も考慮する必要性を新たに示すものとなった。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (42 results)

All 2020 2019 2018 2017 2016

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (25 results) (of which Int'l Joint Research: 12 results,  Invited: 12 results) Book (3 results)

  • [Journal Article] ABCG2 requires a single aromatic amino acid to "clamp" substrates and inhibitors into the binding pocket.2020

    • Author(s)
      Gose T, Shafi T, Fukuda Y, Das S, Wang Y, Allcock A, Gavan McHarg A, Lynch J, Chen T, Tamai I, Shelat A, Ford RC, Schuetz JD.
    • Journal Title

      FASEB Journal

      Volume: 34 Issue: 4 Pages: 4890-4903

    • DOI

      10.1096/fj.201902338rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of the Uptake Transporter Responsible for Distribution of Acotiamide into Stomach Tissue.2020

    • Author(s)
      Hirayama M, Hoshino Y, Yoshii K, Toda R, Kawabata Y, Nakanishi T, Tamai I.
    • Journal Title

      Molecular Pharmaceutics

      Volume: 17 Issue: 4 Pages: 1071-1078

    • DOI

      10.1021/acs.molpharmaceut.9b00894

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Imaging of Hepatic Drug Transporters with [131I]6-β-iodomethyl-19-norcholesterol.2019

    • Author(s)
      Kobayashi M., Nishi K., Mizutani A., Hokama T., Matsue M., Tsujikawa T., Nakanishi T., Nishii R., Tamai I., Kawai K.
    • Journal Title

      Sci. Rep.

      Volume: 9 Issue: 1 Pages: 13413-13413

    • DOI

      10.1038/s41598-019-50049-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of endogenous multidrug resistance 1 and P-glycoprotein expression on anticancer drug resistance in colon cancer cell lines.2019

    • Author(s)
      Washio I, Nakanishi T, Ishiguro N, Bister B, Tamai I.
    • Journal Title

      Biopharmaceutics and Drug Disposition

      Volume: 40 Issue: 1 Pages: 32-43

    • DOI

      10.1002/bdd.2167

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes of drug pharmacokinetics mediated by downregulation of kidney organic cation transporters Mate1 and Oct2 in a rat model of hyperuricemia2019

    • Author(s)
      Nishizawa Kei、Yoda Noriaki、Morokado Fumi、Komori Hisakazu、Nakanishi Takeo、Tamai Ikumi
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 4 Pages: 0214862-0214862

    • DOI

      10.1371/journal.pone.0214862

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of MRP2 as a targetable factor limiting oxaliplatin accumulation and response in gastrointestinal cancer.2019

    • Author(s)
      Myint K, Biswas R, Li Y, Jong N, Jamieson S, Liu J, Han C, Squire C, Merien F, Lu J, Nakanishi T, Tamai I, McKeage M.
    • Journal Title

      Scientific Report

      Volume: 9 Issue: 1 Pages: 2245-2245

    • DOI

      10.1038/s41598-019-38667-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Apple-Derived Nanoparticles Modulate Expression of Organic-Anion-Transporting Polypeptide (OATP) 2B1 in Caco-2 Cells.2018

    • Author(s)
      Fujita D, Arai T, Komori H, Shirasaki Y, Wakayama T, Nakanishi T, Tamai I.
    • Journal Title

      Molecular Pharmaceutics

      Volume: 15 Issue: 12 Pages: 5772-5780

    • DOI

      10.1021/acs.molpharmaceut.8b00921

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sandwich-Cultured Hepatocytes for Mechanistic Understanding of Hepatic Disposition of Parent Drugs and Metabolites by Transporter-Enzyme Interplay.2018

    • Author(s)
      Matsunaga N, Fukuchi Y, Imawaka H, Tamai I.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 46 Issue: 5 Pages: 680-691

    • DOI

      10.1124/dmd.117.079236

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化管トランスポーター基質を利用した経口DDSの現状と今後の展開2018

    • Author(s)
      藤田大地、玉井郁巳
    • Journal Title

      Drug Delivery System

      Volume: 33 Pages: 377-389

    • NAID

      130007604264

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Hyperuricemia enhances intracellular urate accumulation via down-regulation of cell-surface BCRP/ABCG2 expression in vascular endothelial cells.2018

    • Author(s)
      Hisakazu Komori, Kazuyuki Yamada, Ikumi Tamai
    • Journal Title

      Biochim Biophys Acta

      Volume: 1860(5) Issue: 5 Pages: 973-980

    • DOI

      10.1016/j.bbamem.2018.01.006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of equilibrative nucleoside transporters(s) to intestinal basolateral and apical transport of anticancer trifluridine2018

    • Author(s)
      Takahashi K, Yoshisue K, Chiba M, Nakanishi T, Tamai I
    • Journal Title

      Biopharmaceutics & Drug Disposition

      Volume: 39 Issue: 1 Pages: 38-46

    • DOI

      10.1002/bdd.2110

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Revisiting the role of gut wall in the face of orally administered drugs: Why now and to what effect?2017

    • Author(s)
      Rostami-Hodjegan A, Tamai I, Pang S.
    • Journal Title

      Biopharmaceutics & Drug Disposition

      Volume: 38 Issue: 2 Pages: 87-93

    • DOI

      10.1002/bdd.2071

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular localization and characterization of multiple binding sites of organic anion transporting polypeptide 2B1 (OATP2B1) as the mechanism for substrate and modulator dependent drug-drug interaction.2017

    • Author(s)
      Hoshino Y, Fujita D, Nakanishi T, Tamai I.
    • Journal Title

      Med Chem Commun

      Volume: 7 Issue: 9 Pages: 1757-1782

    • DOI

      10.1039/c6md00235h

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Organic Anion Transporting Polypeptide (OATP)2B1 Contributes to Gastrointestinal Toxicity of Anticancer Drug SN-38, Active Metabolite of CPT-11.2017

    • Author(s)
      Fujita D, Saito Y, Nakanishi T, Tamai I.
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 44 Issue: 1 Pages: 1-7

    • DOI

      10.1124/dmd.115.066712

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Regulation of intestinal OATP2B1 by food-derived microRNA through apple nanoparticles2019

    • Author(s)
      Ikumi Tamai, Daichi Fujita, Hisakazu Komori
    • Organizer
      BioMedical Transporter 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulatory effect of fruit-derived nanoparticle on intestinal transporters organic anion transporting polypeptide (OATP) 2B12019

    • Author(s)
      Fujita D, Komori H, Shirasaki Y, Arai T, Iwamoto Y, Wakayama T, Nakanishi T, Tamai I
    • Organizer
      ISEV2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of intestinal OATP2B1 by microRNA contained in apple-derived nanoparticle as cargo.2019

    • Author(s)
      Fujita D, Shirasaki S, Komori H, Tamai I.
    • Organizer
      第34回日本薬物動態学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Laxative effect of apple through modulation of intestinal bile acid transporter ASBT.2019

    • Author(s)
      2)Iwamoto Y, Iwai R, Fujita D, Zhu Q, Aosaki H, Komori H, Tamai I.
    • Organizer
      第34回日本薬物動態学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Food Effect on Intestinal Transporters ASBT and OATP2B1.2019

    • Author(s)
      Tamai I.
    • Organizer
      Meet the Experts: Transporter Conference Seoul 2019,
    • Related Report
      2019 Annual Research Report
  • [Presentation] DDI・DFIによるOATP2B1の活性変動機構の多様性2019

    • Author(s)
      藤田大地、荒井まゆみ、朱秋楠、小森久和、玉井郁巳
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] Drug-Drug and Drug-Food Interactions on Transporters2018

    • Author(s)
      Tamai I
    • Organizer
      CPSA Shanghai 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulatory Effect of Fruit-derived Nanoparticle on Intestinal Transporters2018

    • Author(s)
      Arai T, Shirasaki Y, Komori H, Nakanishi T, Tamai I
    • Organizer
      EB2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mechanisms and Impact of Drug-Drug and Drug-Food Interaction on Transporters2018

    • Author(s)
      Tamai I
    • Organizer
      The 3rd Drug Transporter Forum
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トランスポーター~医薬品の作用・動態~2018

    • Author(s)
      玉井郁巳
    • Organizer
      石川県病院薬剤師会学術講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 高尿酸血症が及ぼす薬物トランスポーター発現ならびに薬物動態変動2018

    • Author(s)
      西澤 慧、依田典朗、諸角芙美、表 早紀、荒川 大、中西猛夫、玉井郁巳
    • Organizer
      第3回北陸高尿酸血症セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] Introduction: ADME-PK Studies for Improved Prediction and Development of Oral Drug Products.2018

    • Author(s)
      Tamai I
    • Organizer
      2018 International Meeting on 22nd MDO and 33rd JSSX
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Down regulation of intestinal bile acid transporter ASBT by apple-derived nanoparticles2018

    • Author(s)
      Iwamoto Y, Fujita D, Arai T, Shirasaki Y, Aosaki H, Arai M, Wakayama T, Komori H, Nakanishi T, Tamaia I
    • Organizer
      2018 International Meeting on 22nd MDO and 33rd JSSX
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 薬物吸収とトランスポーター2018

    • Author(s)
      玉井郁巳
    • Organizer
      第35回 日本TDM学会学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 果物由来ナノ粒子が及ぼす小腸輸送体への影響2018

    • Author(s)
      藤田大地、荒井俊樹、白崎佑磨、岩本結、小森久和、中西猛夫、玉井郁巳
    • Organizer
      第33回人約z学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Regulatory Effect of Fruit-derived Nanoparticle on Intestinal Transporters2018

    • Author(s)
      Daichi Fujita, Toshiki Arai, Yuma Shirasaki, Yui Iwamoto, Hisamazu Komori, Takeo Nakanishi, Ikumi Tamai
    • Organizer
      Experimental Biology 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Drug-Drug and Drug-Food Interaction on Transporters2018

    • Author(s)
      Ikumi Tamai
    • Organizer
      CPSA Shanghai 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanism and Impact of Drug-Drug and Drug-Food Interactions on Transporters2018

    • Author(s)
      Ikumi Tamai
    • Organizer
      3rd Drug Transporter International Forum
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 薬物吸収とトランスポーター2018

    • Author(s)
      玉井郁巳
    • Organizer
      日本TDM学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Food-Drug and Drug-Drug Interactions2017

    • Author(s)
      Ikumi Tamai
    • Organizer
      Meet the Expert, Transporter Conference, 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Effect of Fruit-derived nanoparticle on intestinal transporters2017

    • Author(s)
      Toshiki Arai, Yuma Shirasaki, Daichi Fujita, Takeo Nakanishi, Ikumi Tamai
    • Organizer
      第32回日本薬物動態学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Involvement of intestinal transporter OATP2B1 in gastrointestinal toxicity induced by SN-38, an active metabolite of anticancer irinotecan.2016

    • Author(s)
      Fujita D, Nakanishi T, Tamai I
    • Organizer
      The Globalization Pharmaceutics Education Network(GPEN) 2016
    • Place of Presentation
      Lawrence, Kansas, USA
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Drug-Food Interaction and Evaluation2016

    • Author(s)
      玉井郁巳
    • Organizer
      日本薬物動態学会第31年会
    • Place of Presentation
      松本市
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 食品による薬物の消化管動態影響因子の活性変動の評価2016

    • Author(s)
      Miki Y, Nakanishi T, Tamai I
    • Organizer
      日本薬物動態学会第31回年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] トランスポーターでわかってきた薬物動態と生理機構2016

    • Author(s)
      玉井郁巳
    • Organizer
      日本薬物動態学会第31年会
    • Place of Presentation
      松本
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 臨床薬学テキストシリーズ、循環器/腎・泌尿器/代謝/内分泌、2020

    • Author(s)
      玉井郁巳
    • Total Pages
      381
    • Publisher
      中山書店
    • Related Report
      2019 Annual Research Report
  • [Book] 月刊薬事2016

    • Author(s)
      玉井郁巳
    • Total Pages
      218
    • Publisher
      薬事日報社
    • Related Report
      2016 Annual Research Report
  • [Book] 医療薬学VI薬の体内運命2016

    • Author(s)
      玉井郁巳
    • Total Pages
      195
    • Publisher
      東京化学同人
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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