The effect of febrifugine, the main alkaloidal constituent of an antimalari
al crude drug, Dichroa febrifuga Lour., on protective immunity in mice infe
cted with erythrocytic stage Plasmodium berghei NK65 was investigated. Febr
ifugine was administered orally, at a dose of 1 mg/kg/day, to mice before a
nd/or after they were infected intraperitoneally with 2 X 10(6) parasitized
red blood cells. Then, mortality and the levels of parasitemia and plasma
NO3- [a degradation product of nitric oxide (NO)] were monitored. Febrifugi
ne significantly reduced the mortality and the level of parasitemia. The pl
asma NO3- concentration began to rise within 2 days after treatment with fe
brifugine and declined to normal in 2 days when the mice were treated orall
y with febrifugine once a day for 3 consecutive days before parasite infect
ion. This antimalarial activity of febrifugine was reduced by both N-G-mono
methyl-L-arginine and aminoguanidine. These results indicate that the incre
ased production of NO by febrifugine plays an important role in host defens
e against malaria infection in mice. (C) 1999 Elsevier Science Inc.