1. Possible Artefacts in the in vitro Determination of Antimalarial Activity of Natural Products that Incorporate into Lipid Bilayer: Apparent Antiplasmodial Activity of Dehydroabietinol, a Constituent of Hyptis suaveolens
- Author
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Dan Staerk, Archibald Sittie, Thomas Jensen, Jerzy W. Jaroszewski, Henry Hägerstrand, Jette Christensen, Carl Erik Olsen, Trine Staalsø, Patrick Ekpe, and Hanne L. Ziegler
- Subjects
Erythrocytes ,Stereochemistry ,Lipid Bilayers ,Plasmodium falciparum ,Pharmaceutical Science ,Pharmacognosy ,Analytical Chemistry ,Antimalarials ,Inhibitory Concentration 50 ,Drug Discovery ,Hyptis suaveolens ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Lipid bilayer ,Cell Size ,Pharmacology ,Biological Products ,Lamiaceae ,biology ,Organic Chemistry ,Chloroquine ,Biological activity ,biology.organism_classification ,In vitro ,Microscopy, Electron ,Red blood cell ,medicine.anatomical_structure ,Complementary and alternative medicine ,Biochemistry ,Mechanism of action ,Abietanes ,Molecular Medicine ,Diterpenes ,medicine.symptom ,Artifacts ,Sesquiterpenes - Abstract
Dehydroabietinol isolated from Hyptis suaveolens (L.) Poit. was found to inhibit growth of chloroquine-sensitive as well as chloroquine-resistant strains of Plasmodium falciparum cultivated in erythrocytes in vitro (IC 50 26-27 microM). However, erythrocytes exposed to dehydroabietinol were transformed in a dose-dependent manner towards spherostomatocytic forms with concomitant formation of endovesicles, as disclosed by transmission electron microscopy. The erythrocyte shape alterations caused by dehydroabietinol correlated well with its apparent IC 50 value. Thus, dehydroabietinol incorporates into the erythrocyte membrane, and since invasion and survival of Plasmodium parasites is known to depend on the function of the erythrocyte membrane, the observed antiplasmodial effect of dehydroabietinol is presumably an indirect effect on the host cell. Because of these findings, microscopic investigations should be generally used to support claims of antimalarial effects of apolar natural products.
- Published
- 2002
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