| Project/Area Number |
05558082
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Bioorganic chemistry
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| Research Institution | University of Tokushima |
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Principal Investigator |
TAKAISHI Yoshihisa University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (60035558)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yukihisa Otsuka Pharmaceutical Co., Researcher, 研究員
NAKANO Kimiko University of Tokushima, Faculty of Pharmaceutical Sciences, Research Assistant, 薬学部, 助手 (20136279)
SHISHIDO Kozo University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20006349)
SHIBUYA Masayuki University of Tokushima, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40027066)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥17,500,000 (Direct Cost: ¥17,500,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1993: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | rheumatoid arthritis / interleukin-1 / Celastraceae / Tripterygium / triptoquinone / diterpene / quinoide / NO / callus / 慢性関節リウマチ / トリテルペン / 植物組織培養 / 抗炎症 |
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| Research Abstract |
Tripterygium wilfordii Hook (Celastraceae) has been used as anticancer drug and an insecticide by the Chinese for hundreds of years. Recently, this plant has been used to treat rheumatoid arthritis and spondy litis in some Chinese clinics. We started the study of isolation of the active priciples from T.wilfordii Hook fil var. regelii. For the in vitro assay system, we used the inhibition effects of interleukin-1 (IL-1) release.
In rheumatoid arthritis, it is reported that there is a strong relationship between production of IL-1 by the synovium and degree of inflammation of the arthricular synovial membrane.
It is therefore considered that the inhibition of excessive IL-1 release from cell could block various physiological activities. Bioassay-guided exploration led to the isolation of several structurally novel diterpenoid quinones. These quinones (we named triptoquionones A-G) proved to markedly inhibit the release of IL-1alpha and -1beta from lipopolysaccharide stimulated human peripheral mononuclear cells. The structures of these compound were elucidated on the basis of spectroscopic and chemical evidence.
The most promising of these diterpenoids, from the standpoint of potential utility for treatment of rheumatoid arthritis, is triptoquinone A,which has progressed to further biological tests in vitro. So, we attempted the total synthesis of thriptoquinone A (TQA) and succeed an efficient first total synthesis.
A significant inhibitory activity of TQA for adjuvant-induced arthritis was confirmed in rat. TQA did not show serious poisoning. TQA inhibited NOs induction primed by LPS.
We isolated seven new triterpenoids from T.wilfordii, some of which showed the inhibition of IL-1 release. We attempted the preparation of callus and hairly root from T.wilfordii, and studied the constituents of callus.
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