Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
Parasitology (including Sanitary zoology)
|Research Institution||Kyorin University|
OHSAKI Takako Kyorin University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (90255406)
HARUKI Kosuke National Defence medical college, Faculty of Medicine, Assistant Professor, 医学教育部, 助手 (30286421)
|Project Period (FY)
2003 – 2004
Completed(Fiscal Year 2004)
|Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2004 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2003 : ¥2,200,000 (Direct Cost : ¥2,200,000)
|Keywords||Malaria / Chloroquine / Reversal / Alkaloid / Cepharanthin / Pseudomonas aeruginosa / tetraphenylphosphonium / クロロキン耐性 / リバーサル / 薬剤排出 / 緑膿菌 / 新規抗マラリア薬 / TPP|
we investigated the reversal effect of cepharanthin against drug resistant Pseudomonas aeruginosa.
Result : There is no reversal effect on efflux pump of drug resistant Pseudomonas aeruginosa.
1 Investigation of reversal by Cepharanthin (CP) and accumulation.
Results : Each alkaloids reversed chloroquine (CQ) sensitivity and accumulated CQ in to the cell. The results also showed CQ sensitivity is enhanced by accumulation of CQ.
2 Time course of CQ accumulation with CP.
Results : accumulation of CQ increased dramatically compare with control.
3 Investigation of CQ efflux from parasite with CP.
Results : The efflux of CQ from parasite inhibited with CP.
4 Membrane potential change by CP.
Results : Membrane potential decreased by CP.
5 Investigation of Tetraphenylphosphonium (TPP) as a model of CP as membrane potential modulator.
Results : TPP modulated membrane potential of parasite food vacuole and changed sensitivity.
6 Screening of anti-malarial agent.
Results : We discovered a existent drug which has anti-malarial activity.
Conclusion : CP enhanced the sensitivity of CQ by accumulating CQ in the cell due to inhibiting efflux of CQ. The drug efflux pump of Pseudomonas aeruginosa was not enhanced by CP. TPP may be a model of CP effect as membrane potential modulator. We discovered an existent drug which has anti-malarial activity whilst this experimental project.