Treatment of Plasmodium chabaudi Parasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System

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 be...

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Bibliographic Details
Published inJournal of Parasitology Research Vol. 2013; no. 2013; pp. 59 - 69
Main Authors Neto, Zoraima, Machado, Marta, Lindeza, Ana, do Rosário, Virgílio E., Gazarini, Marcos L., Lopes, Dinora
Format Journal Article
LanguageEnglish
Published Cairo, Egypt Hindawi Limiteds 2013
Hindawi Puplishing Corporation
Hindawi Publishing Corporation
John Wiley & Sons, Inc
Hindawi Limited
Subjects
Analysis
Antimalarials
Complications and side effects
Control
Drug resistance
Drug therapy
Health aspects
Malaria
RNA
Ubiquitin
Portugal
Germany
Spain
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Summary: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.
Bibliography:Academic Editor: Xin-zhuan Su
ISSN:2090-0023
2090-0031
DOI:10.1155/2013/429736