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SERCHING FOR DISCOVERY OF RHEUMATOID ARTHRITIS DRUG FROM TRIPTERYGIUM WILFORDII.

Research Project

Project/Area Number 10557209
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Chemical pharmacy
Research InstitutionUniversity of Tokushima

Principal Investigator

TAKAISHI Yoshihisa  University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60035558)

Co-Investigator(Kenkyū-buntansha) ONO Yukihisa  Otsuka Pharmaceutical Company, Researcher, 医薬第3研究所, 研究員
MURAKAMI Koutarou  University of Tokushima, Faculty of Pharmaceutical Sciences, Assistnt Prof., 薬学部, 助手 (10035553)
KAWAZOE Kazuyoshi  University of Tokushima, Faculty of Pharmaceutical Sciences, Lecture, 薬学部, 講師 (00248296)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,500,000 (Direct Cost: ¥11,500,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsRHEUMATOID ARTHRITIS / CYTOKINE / Tripterygium wilfordii / Triterpene / Diterpene / Interleukin-1 / Natural Product / 電公藤 / アルカロイド / 毛状根培養
Research Abstract

In recently years, a refined extract from the root xylem of Tripterygium wilfordii (TII) has been used in the clinical treatment of rheumatoid arthrits, and for other inflammatory and autoimmune diseases, including systermic lupus erythemasus etc. However, the precise mechanism of the therapeutic effect of TII has not been completely delineated. We has started work on the isolation of T.hypoglaucum and T.wildfordii and the TII extract to discover new drug for Rheumatoid Arthrits desease. We isolated five new triterpenes, two new diterpenes, and twelve new sesquiterpene pyridine alkaloids, as well as thirty-three known compounds from the root outer barks of T.hypoglaucum. From the TII extract of T.wilfordii, seven new triterpenes, four new diterpenes, twenty new sesquiterpene pyridine alkaloids, as well as fifty-six known compounds. In the bioactive screening experiment for isolated compoinds, the auther examined inhibitory effect on cytokine production and anti-HIV activity. Three compounds showed extreamely potent inhibitory effect on cytokine production from LPS stimulated human peripheral mononuclea cellscompared with reference compound. and sesquiterpene alkaloid inhibited HIV replication in H9 lymphocytes with therapeutic index value of>1000, this compound is a new class of potent anti-HIV agents from natural source.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] E.Yesilada: "Effects of the Turkish Subspecies of Viscum album on Macrophage-derived Cytokines"J.Ethnopharmacology. 61. 195-200 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Duan: "Sesquiterpene Alkaloids from Extracts of Tripterygium wilfordii"Chem.Pharm.Bull.. 47. 1664-1667 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Duan: "Immunosuppeessive Diterpenoids from Tripterygium wilfordii"J.Nat.Prod.. 62. 1522-1525 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Taninaka: "Terpenoids and Aromatic Compounds from Daphre oleoides spp, oleoides"Phytochemistry. 52. 1735-1738 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] B-N.Su: "Macrophyllols A and B, Two Unusual Novel Sesquiterpenoids and Monoterpene Dimers from the Bark Inula macro phylla"Organic Letters. 2. 493-496 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] R.Fujita: "Terpenoids from Tryperygium wilfordii"Phytochemistry. 53. 715-722 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yesilada E., Deliorman D., Ergun F., Takaishi Y., Ono Y.: "Effects of the Turkish Subspecies of Viscum album on Macrophage-derived Cytokines."J.Ethnopharmacology. 61. 195-200 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Duan H., Takaishi Y.: "Sesquiterpene Alkaloids from Extraets of Tripterygium wilfordii"Chem.Pharm.Bull.. 47. 1664-1667 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Duan H., Takaishi Y., Momota H., Ohmoto Y., Takai T., Jia Y., Li D.: "Immunosuppressive Diterpenoids from Tripterygium wilfordii."J.Natural Products. 62. 1522-1525 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Taninaka H., Takaishi Y., Honda G., Imakura Y., Sezik E., Yesilada E.: "Terpenoids and Aromatic Compounds from Daphne oleoides ssp. oleoides."Phytochemistry. 52. 1735-1738 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Su B-N., Takaishi Y., Tori M., Takaoka S., Honda G., Itoh M., Takeda Y., Kodzhimatov O.K., Ashurmetov O.: "Macrophyllols A and B, Two Unusual Novel Sesquiterpeneand Monoterpene Dimers from the Bark of Inula macrophylla."Organic Letters. 2. 493-496 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujita R., Duan H., Takaishi Y.: "Terpenoids from Tripterygium hypoglancum."Phytochemistry. 53. 715-722 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] B-N.Su: "Macrophyllos A and B, Two Unusual Novel Sesgui Ferpenoid and Monoferpene Dimers from Bark Inula macrophylla"Organic Letlers. 2巻. 493-496 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] B.N.Su: "Macrophyllidimers A and B, Two Novel Sesquiferpens Dimers from the Bark of Inulamacrophylla "Tetrahedron Letlers. 41巻. 1475-1479 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Duan: "Sespuitacpens Alkaloids from Tripterygium hypoglanoua and Tripterygium wilfordii : A New Closo of Potent Anti HIV Agents"J.Natural Producto. 63巻. 357-361 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] C.Bei: "Prenylated Bengoic Acid Deivatives from Ferula Kuhistanica"J.Natural Producto. 63巻. 362-365 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] R.Fujita: "Terpenoido from Tripterygium hypoglancum"Phytochemistry. 53巻. 715-722 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Duan: "Terpenoido from Tripterygium wilfordii"Phytochemistry. 53巻. 805-810 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Duan,Y.Takaishi,M.Bando,M.Kido,I.Imakura,K-H,Lee: "Novel sesquiterpenes Ester with alkaloid and Monoterpene and Related Compounds from Tripterygium hypoglancum"Tetrahedron letters. 40・15. 2969-2972 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] B.Chen,H.Duan,Y.Takaishi: "Triterpene Caffeoyl esters and diterpenes from Celabtras stephanotifolius"Phytochemistry. 51. 683-687 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Duan,Y.Takaishi,Y.Jia.: "Sesquiterpene Alkaloids from Extract of Tripterygium wilfordii"Chem.Pharm.Bull. 47・11. 1664-1667 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Duan,Y.Takaishi,H.Momota,Y.Ohmoto,T.Takai,Y.Jia,D.Li: "Immunosuppressive Diterpenoids from Tripterygium wilfordii"J.Natural Products. 62・11. 1522-1525 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nakano: "Terpenoids in Transformed Root Culfure of Tripterygium wilfordii" Phytochemisty. 49・6. 1821-1824 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Duan: "Structures of Sesquiterpene Polyol Alkaloido from Tripterygium hypoglaucum" Phytochemistry. 49・7. 2185-2189 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Duan: "Novel Sesquiterpene Esters with Alkaloid and Monoterpene and Related Compounds from Tripterygium wilfordii" Tetrahedron letters. (in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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