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Malaria treatment (References: PubMed, Google, Ginsburg H and Golenser J publications)

Malaria treatment (References: PubMed, Google, Ginsburg H and Golenser J publications). CHING-HAO (Artemisinin) is isolated from Artemisia annua and used in chinese medicine. Trophozoite- EM. Labile iron in P.falciparum infected erythrocytes induce fragmentation of DNA.

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Malaria treatment (References: PubMed, Google, Ginsburg H and Golenser J publications)

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  1. Malaria treatment (References: PubMed, Google, Ginsburg H and Golenser J publications)

  2. CHING-HAO (Artemisinin) is isolated from Artemisia annua and used in chinese medicine

  3. Trophozoite- EM

  4. Labile iron in P.falciparum infected erythrocytes induce fragmentation of DNA Fe2+ + H2O2 ----> Fe3+ + .OH + OH-

  5. Ridley RG, Nature. 2003, 424 (6951): 887-9

  6. Artemisinin inhibits plasmodia by two mechanisms: • Production of free radicals which affects different macromolecules. • 2. Specific interference with PfATP6 (Ca-2+ATPase (SERCA)). This interference is also mediated by iron induced damage. • Thapsigargin is an inhibitor of SERCA, has structural similarity to artemisinin, lacks peroxide bridge and interferes with the anti-plasmodial activity of artemisinin. • Iron chelator (Desferal) abrogates artemisinin effect on SERCA. • The first mechanism explains the non-specific effect on various eukaryotic cells (ED50 mM). The second one explains the specificity towards Plasmodium falciparum (ED50 nM).

  7. Spread of chloroquine resistance

  8. The Mechanism of Accumulation of Chloroquine in the Parasite Food Vacuole Chloroquine travels down a pH gradient and inside the parasite becomes diprotonated. This form of the drug (shown in blue) is impermeable to biological membranes.On the right of the figure is a generic structure of a parasite targeted artemisinin derivative

  9. Food vacuole Hb 1 2 { } Hb FP HZ Glu Cys Gly Parasite Host cell CQ 9 FP:CQ de novo synthesis 8 K+ 11 FP Na+ NADP NADPH GSH GSSG HMS 7 GR 6 3 Enzyme 10 CQ - Fe3+ Fe2+ O2+H+ O2 H2O2 O2+H2O GSH GSSG Reductone GPx 4 5

  10. V H P V H S R

  11. Table 1. Reported polymorphisms on the Plasmodium falciparum chloroquine resistance transporter gene, pfcrt, on chromosome 7. Wernsdorfer, Curr Opin Infect Dis, 2003, 16, 553-558.

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