Abstract
Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed. In vivo efficacy of curcumin was studied in BALB/c mice infected with Plasmodium chabaudi clones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs). Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group's 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.
Highlights
Malaria remains a major cause of mortality and morbidity especially in sub-Saharan Africa
The aim of this study was to determine the in vivo efficacy of curcumin alone or in combination: curcumin/piperine/chloroquine and curcumin/piperine/artemisinin in order to clarify their drug interactions in Plasmodium chabaudi resistant parasites
The acute toxicity studies revealed that curcumin was nontoxic to mice even at 2 g/kg/bw (Table 1); mice survived for 14 days with no signs of toxicity
Summary
Malaria remains a major cause of mortality and morbidity especially in sub-Saharan Africa. Children under five and pregnant women remain the most vulnerable groups afflicted by this disease [1]. Control programs are strongly affected by resistance to insecticides and to antimalarials, including the recently implemented combination therapies with artemisinin and its derivatives [2, 3]. Development of new antimalarial drugs is necessary though expensive and time consuming, and a number of potential antimalarials exist either derived from plants or as new synthetic compounds [4]. The active compound derived from the plant Curcuma longa, has anticancer, antiinflammatory, antiviral, and antimalarial activity [5,6,7,8,9,10]. Curcumin has shown potent activity against other organisms including: Schistosoma mansoni adult worms, Cryptosporidium parvum, and Trypanosoma cruzi [8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
