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.
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.
Ziegler
Hanne L
HL
Jensen
Thomas Høgh
TH
Christensen
Jette
J
Staerk
Dan
D
Hägerstrand
Henry
H
Sittie
Archibald A
AA
Olsen
Carl Erik
CE
Staalsø
Trine
T
Ekpe
Patrick
P
Jaroszewski
Jerzy W
JW
D045784:Abietanes; D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D016477:Artifacts; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004224:Diterpenes; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D020128:Inhibitory Concentration 50; D019686:Lamiaceae; D008051:Lipid Bilayers / Q000378:metabolism; D008854:Microscopy, Electron; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D045784:Abietanes; D000962:Antimalarials; D001688:Biological Products; D004224:Diterpenes; D008051:Lipid Bilayers; D012717:Sesquiterpenes; D002738:Chloroquine; C465098:dehydroabietinol