Objective: To investigate the activity of daphnetin(DPNT) against the exo-erythrocytic stage of rodent malaria.
Methods: Groups of ten male ICR mice were infected by intraperitoneal injection with sporozoites of P. yoelii. Mice were administered daphnetin 0.5 hr postinfection on d0 and once per day for three additional consecutive days(d1-d3) by the i.g. route. The effects of daphnetin at various dosages and those of the combination of daphnetin with primaquine were assessed by the number of mice with negative Giemsa-stained slides from tail blood on the seventh day after infection and by the average number of red blood cells (RBC) infected in 1,000 RBC observed on the eleventh or twelfth day after infection. We also observed the effect of daphnetin on the concentration of Hb in ICR mice.
Results: Daphnetin exhibited no detectable antimalarial effect on the exo-erythrocytic stage of P. yoelii, while the antimalarial efficacy of DPNT 50 mg/(kg.d) combined with 5 mg/(kg.d) PQ, was comparable to PQ 10 mg/(kg.d) x 4 d i.g. in mice infected with sporozoites of P. yoelii. The concentration of Hb in ICR mice administered with DPNT 50 mg/(kg.d) x 4 d decreased on the eighth day after administration.
Conclusion: Daphnetin alone showed no anti-exoerythrocytic activity in vivo. The combination of DPNT 50 mg/(kg.d) with PQ 5 mg/(kg.d) showed promising antimalarial efficacy comparable to that of PQ 10 mg/(kg.d). Administration of DPNT caused anemia in ICR mice.