| Project/Area Number |
11672101
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
KIUCHI Fumiyuki Kyoto University, Graduate School of Pharmaceutical Sciences Associate Professor, 薬学研究科, 助教授 (60161402)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMASHIMADA Junko Juntendo University, School of Medicine Lecturer, 医学部, 講師 (20211964)
AOKI Takashi Juntendo University, School of Medicine Professor, 医学部, 教授 (20053283)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | trypanosomiasis / Trypanosoma cruzi / Hela infection assay / natural medicines / Alpinia galanga / Laurus nobilis / Desmos dasymachalus / dasymachaline-N-oxide / Vietnam / 1′-acetoxychavicol acetate / dasymacharine-N-oxide / 天然薬物 / ローレル / monoterpene / sesquiterpene lactone |
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| Research Abstract |
1. Antitrypanosomal screening of natural medicines
Antitrypanosomal activity of natural medicines used in Asian countries was evaluated by an assay system, which models the infection of Trypanosoma cruzi to human cells (HeLa cell). Leaves of Laurus nobilis, seeds of Psoralea corylifolia, and fruits of Piper longum showed strong activity. About 100 natural medicines used in Vietnam were also tested for trypanocidal activity against epimastigotes of T.cruzi. In this assay, rhizomes of Alpinia galanga, whole plant of Dendrobium nobile, roots of Paris polyphilla, etc. showed strong activity.
2. Identification of antitrypanosomal principles
The antitrypanosomal principles of some of the above natural medicines were identified. From the leaves of Laurus nobilis, two sesquiterpene γ-lactones (dehydrocostus lactone, zaluzanin D) and a monoterpene hydroperoxide were isolated. The monoterpene inhibited the infection of trypomastigotes to HeLa cells by 98% as well as the proliferation of amastigotes in HeLa cells by 84% at 1 μg/ml without any toxicity to HeLa cells at 10 μg/ml. From the rhizomes of Alpinia galanga, eight phenylpropanoids, including its major constituent 1'-acetoxychavicol acetate, were isolated as active principles. Comparison of the activity of these phenylpropanoids suggested that the reactivity of the double bond in these compounds is important for the activity. From the roots of Desmos dasymachalus, which are used for dysentery in Sarawak, dasymachaline and its N-oxide were isolated as active components. Trypanocidal activity of the N-oxide was about 10 times stronger than the original alkaloid. This is the first report of trypanocidal activity of an alkaloid N-oxide. This finding will open an access to a new class of natural products having potent antitrypanosomal activity.
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