Plasmodium berghei: antiparasitic effects of orally administered hypoestoxide in mice.
Hypoestoxide (HE) is a diterpene isolated from Hypoestes rosea (Acanthaceae), a plant indigenous to Nigeria. Previous studies demonstrated that HE exhibited potent anti-inflammatory and anti-cancer activities in well established animal models but weak in vitro activities in both the anti-inflammation and anti-cancer in vitro screening systems. We now report a similar observation in the in vitro and in vivo screening systems for antimalarial activity. The results indicate that while HE exhibits a relatively weak in vitro activity (IC(50) = 10 microM versus 0.11 microM for chloroquine) against different strains of cultured P. falciparum parasites, the dose of HE required to reduce parasitemia by 90% in Plasmodium berghei-infected mice, is much lower than standard antimalaria drugs (SD(90) = 250 microg/kg versus 5mg/kg for chloroquine). Furthermore, lower doses of HE were much more effective than higher doses in inhibiting parasite development. The implications of these findings are discussed.
Ojo-Amaize
Emmanuel A
EA
Paraquest, Inc., P.O. Box 998, Bloomington, CA 92316-0998, USA. ojoamaize@aol.com
Nchekwube
Emeka J
EJ
Cottam
Howard B
HB
Oyemade
Olusola A
OA
Adesomoju
Akinbo A
AA
Okogun
Joseph I
JI
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects*
D000962:Antimalarials; D004224:Diterpenes; C432343:hypoestoxide; D005978:Glutathione