piperidines and Parasitemia

Parasitemia patterns, survival and cytokine levels of Plasmodium berghei NK65-infected BALB/c mice, treated orally with the alkaloidal mixture of febrifugine and isofebrifugine at a dose of 1 mg/kg twice a day for 4 consecutive days were monitored. Whereas the untreated mice showed a progressive increase in parasitemia and ultimate death, the alkaloid mixture-treated group showed a transient suppression of parasitemia during the course of treatment. However, the parasitemia increased on discontinuation of treatment, leading to earlier death of mice in the treated group than in the infected but untreated controls. Mice in the infected but untreated group displayed a significant elevation in serum IFN-gammay levels during the first week post-infection (pI) and from Day 14 pI, relative to the levels in the uninfected controls. In contrast, although mice in the alkaloid mixture-treated group displayed no significant elevation in serum IFN-gamma levels during the first week pI, they showed considerable levels on Day 14 pI. There were no significant differences in serum IL-4 levels among the groups. The titers of the parasite-specific IgG1, IgG2a, IgG2b and IgG3 were significantly elevated from Day 11 pI in both the treated and untreated groups. There was a significant difference in survival duration between the IFN-gamma-/- mutant and BALB/c mice. IFN-gamma-/- mutant mice showed a decrease in parasitemia levels while receiving medication, which was significantly lower than those of the treated BALB/c mice. The results of the present study suggest that although IFN-gamma is significant for protective immunity in mice with malaria infection, it may play an adverse role post-medication, causing earlier mortality of treated BALB/c mice.

Topics: Animals; Antibodies, Protozoan; Antigens, Protozoan; Antimalarials; Interferon-gamma; Interleukin-4; Malaria; Male; Mice; Mice, Inbred BALB C; Parasitemia; Piperidines; Plasmodium berghei; Quinazolines

Recent studies have proposed curcumin as a potential partner for artemisinin in artemisinin combination therapies to treat malaria infections. The efficacy of curcumin alone and in combination with artemisinin was evaluated on a clone of Plasmodium chabaudi selected for artemisinin resistance in vivo. The addition of piperine as an enhancer of curcumin activity was also tested. Results indicated that curcumin, both alone and in combination with piperine had only a modest antimalarial effect and was not able to reverse the artemisinin-resistant phenotype or significantly affect growth of the tested clone when used in combination with artemisinin. This is in contrast with previous in vivo work and calls for further experimental evaluation of the antimalarial potential of curcumin.

Topics: Administration, Oral; Alkaloids; Animals; Anti-Infective Agents; Artemisinins; Benzodioxoles; Biological Availability; Curcumin; Drug Resistance; Drug Therapy, Combination; Malaria; Male; Mice; Parasitemia; Piperidines; Plasmodium chabaudi; Polyunsaturated Alkamides

The effect of febrifugine, the main alkaloidal constituent of an antimalarial crude drug, Dichroa febrifuga Lour., on protective immunity in mice infected with erythrocytic stage Plasmodium berghei NK65 was investigated. Febrifugine was administered orally, at a dose of 1 mg/kg/day, to mice before and/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. Febrifugine significantly reduced the mortality and the level of parasitemia. The plasma NO3- concentration began to rise within 2 days after treatment with febrifugine and declined to normal in 2 days when the mice were treated orally with febrifugine once a day for 3 consecutive days before parasite infection. This antimalarial activity of febrifugine was reduced by both N(G)-monomethyl-L-arginine and aminoguanidine. These results indicate that the increased production of NO by febrifugine plays an important role in host defense against malaria infection in mice.

Topics: Animals; Antimalarials; Drug Interactions; Enzyme Inhibitors; Malaria; Male; Mice; Mice, Inbred ICR; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Parasitemia; Piperidines; Plasmodium berghei; Quinazolines