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薬用植物から難治性生活習慣病の治療薬シーズの開拓と天然分子プローブの創製

Research Project

Project/Area Number 16073221
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Science and Engineering
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

吉川 雅之  Kyoto Pharmaceutical University, 薬学部, 教授 (90116129)

Co-Investigator(Kenkyū-buntansha) 松田 久司  京都薬科大学, 薬学部, 准教授 (40288593)
Project Period (FY) 2004 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥25,200,000 (Direct Cost: ¥25,200,000)
Fiscal Year 2007: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywords薬用植物 / 生活習慣病 / 抗アレルギー作用 / 構造活性相関 / 分子プローブ / 伝承薬 / 甘茶 / 大良姜 / ローズヒップ / Erycibe expansa / アポトーシス誘導活性 / Camellia sinensis / Saussurea medusa / Angelica furcijuga / 抗肥満作用 / 抗糖尿病作用 / 茶花 / Nigella sativa / セイジ / Alpinia galanga / Curcuma zedoaria
Research Abstract

本研究では,研究対象とする薬用植物として,伝承薬効が確実で食経験があるなど安全性が確立しているものを現地調査から厳選し探索資源とする.そして,in vitroやin situ系アッセイを組み合わせた新しい総合評価系を構築応用して,特に,1)肥満や2型糖尿病の予防,治療物質,2)I型アレルギー抑制物質,3)癌増殖過程における癌細胞の浸潤や転移の抑制物質を探索,解明するとともに構造と活性相関を明らかにする.さらに,分子プローブを創製するなどして分子レベルでの作用メカニズムの解明を目標ととしている.平成19年度は,甘茶の主要なイソクマリン成分hydrangeno1が,3T3-L1細胞の脂肪細胞への分化誘導促進,adiponectinの産生やPPAR-γmRNAの発現増加,2型糖尿病モデルKK-A^yマウスでの血糖降下作用などを示すことを見いだした.その作用機序の解明を試みた結果,少なくともPPAR-γアゴニスト作用は全く認められないにもかかわらず,類似の作用を示すことが明らかとなった.また,甘茶の抗アレルギー活性成分thunberginol Bが細胞内シグナル伝達系において,ERKを介したパスウェイに影響を与えていることを明らかにするなど,その作用機序について知見を得ることができた.さらに,大良姜の-酸化窒素産生抑制活性成分l'S-1'-acetoxychavicol acetateやthunberginol B誘導体の分子プローブの創製を試み,いくつかの興味深い知見を得た.その他,中国産の茶花(Camellia sinensis)やデイジーフラワー(Bellis perennis,花部)のサポニン成分から脱穎粒抑制作用や血中中性脂質上昇作用を見いだすなど,平成19年度の当初計画をほぼ達成したものと考える.

Report

(4 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2008 2007 2006 2005 2004

All Journal Article (22 results) (of which Peer Reviewed: 3 results) Presentation (1 results)

  • [Journal Article] Inhibitory effects of thunberginols A and B isolated from Hydrangeae Dulcis Folium on mRNA expression of cytokines and on activation of activator protein-1 in RBL-2H3 cells.2008

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Phytomedicine 15巻

      Pages: 177-184

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New type of anti-diabetic compounds from the processed leaves of Hydrangea macrophylla var. thunbergii (Hydrangeae Dulcis Folium).2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg. Med. Chem. Lett. 17

      Pages: 4972-4976

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Medicinal flowers. XIV. New acylated oleanane-type triterpene oligoglycosides with antiallergic activity from flower buds of chinese tea plant (Camellia sinensis).2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem. Pharm. Bull. 55巻

      Pages: 598-605

    • NAID

      110006241824

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bioactive constituents from Chinese natural medicines. XX. Inhibitors of antigen-induced degranulation in RBL-2H3 cells from the seeds of Psoralea corylifolia2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 55巻

      Pages: 106-110

    • NAID

      110006151443

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitory effects of thunberginols A, B, and F on degranulations and releases of TNF-α and IL-4 in RBL-2H3 cells2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Biol.Pharm.Bull. 30巻

      Pages: 388-392

    • NAID

      110006162866

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rotenoids and flavonoids with anti-invasion of HT1080, anti-proliferation of U937, and differentiation-inducing activity in HL-60 from Erycibe expansa2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem. 15巻

      Pages: 1539-1546

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structures of Steroidal Alkaloid Oligoglycosides, Robeneosides A and B, and Antidiabetogenic Constituents from the Brazilian Medicinal Plant Solanum lycocarpum2007

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      J.Nat.Prod. 70巻

      Pages: 210-214

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Pseudoguaiane-type sesquiterpenes and inhibitors on nitric oxide production from Dichrocephala integrifolia2006

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Tetrahedron 62巻

      Pages: 6435-6442

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Phenylethanoid oligoglycosides and acylated oligosugars with vasorelaxant activity from Cistanche tubulosa2006

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem. 14巻

      Pages: 7468-7475

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Structures of new flavonoids, erycibenins D, E, and F, and NO production inhibitors from Erycibe expansa originating in Thailand2006

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 54巻

      Pages: 1530-1534

    • NAID

      110004836472

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Inhibitors of nitric oxide production from the flowers of Angelica furcijuga : structures of hyuganosides IV and V2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 53

      Pages: 387-392

    • NAID

      10016652965

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Structure-activity relationships of 1'S-1'-acetoxychavicol acetate for inhibitory effect on NO production in lipopolysaccharide-activated mouse peritoneal macrophages2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem.Lett. 15

      Pages: 1949-1953

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 1'S-I'-acetoxychavicol acetate as a new type inhibitor of interferon-β production in lipopolysaccharide-activated mouse peritoneal macrophages2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem. 13

      Pages: 3289-3294

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Floratheasaponins A-C, acylated oleanane-type triterpene oligoglycosides with anti-hyperlipidemic activities from flowers of the tea plant (Camellia sinensis)2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      J.Nat.Prod. 68

      Pages: 1360-1365

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bioactive constituents from Chinese natural medicines. XV. Inhibitory effect on aldose reductase and structures of saussureosides A and B from Saussurea medusa2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 53

      Pages: 1416-1422

    • NAID

      10016784327

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bioactive saponins and glycosides. XXIII. Triterpene saponins with gastroprotective effect from the seeds of Camellia sinensis -Theasaponins E_3, E_4, E_5, E_6, and E_7-2005

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 53

      Pages: 1559-1564

    • NAID

      110004049476

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Novel Dolabellane-Type Diterpene Alkaloids with Lipid Metabolism Promoting Activities from the Seeds of Nigella sativa2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Org.Lett. 6

      Pages: 869-897

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nigellamines A_3, A_4, A_5, and C, New Dolabellane-Type Diterpene Alkaloids, with Lipid Metabolism-Promoting Activities from the Egyptian Medicinal Food Black Cumin2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Chem.Pharm.Bull. 52

      Pages: 494-497

    • NAID

      110003615601

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Structures of New Sesquiterpenes and Hepatoprotective Constituents from the Egyptian Herbal Medicine Cyperus longus2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      J.Nat.Prod. 67

      Pages: 569-576

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Carnosic Acid, a New Class of Lipid Absorption Inhibitor from Sage2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem.Lett. 14

      Pages: 1943-1946

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-allergic Activity of Stilbenes from Korean Rhubarb (Rheum undulatum L.) : Structure Requirements for Inhibition of Antigen-Induced Degranulation and Their Effects on the Release of TNF-α and IL-4 in RBL-2H3 Cells2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem. 12

      Pages: 4871-4876

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-allergic Principles from Thai Zedoary : Structural Requirements of Curcuminoids for Inhibition of Degranulation and the Release of TNF-α and IL-4 in RBL-2H3 Cells2004

    • Author(s)
      Masayuki Yoshikawa
    • Journal Title

      Bioorg.Med.Chem. 12

      Pages: 5891-5898

    • Related Report
      2004 Annual Research Report
  • [Presentation] 甘茶成分thunberginol類の合成と抗アレルギー活性-構造活性相関および作用様式-2007

    • Author(s)
      吉川雅之
    • Organizer
      第49回天然有機化合物討論会講演要旨集
    • Place of Presentation
      札幌コンベンションセンター(札幌市)
    • Year and Date
      2007-09-20
    • Related Report
      2007 Annual Research Report

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Published: 2004-04-01   Modified: 2018-03-28  

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