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Antimicrobial Agents and Chemotherapy, March 2009, p. 1100-1106, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01175-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Properties of Ellagic Acid in Malaria Treatment{triangledown}

Patrice Njomnang Soh,1,2 Benoît Witkowski,1,2 David Olagnier,1 Marie-Laure Nicolau,1,2 Maria-Concepcion Garcia-Alvarez,3 Antoine Berry,1 and Françoise Benoit-Vical1,2*

Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire Toulouse, TSA-50032, 31059 Toulouse 9, France, et Faculté de Médecine de Rangueil, Université de Toulouse, 31059 Toulouse Cedex 9, France,1 CNRS, Laboratoire de Chimie de Coordination UPR8241, 205 Route de Narbonne, F-31077 Toulouse, France, and Université de Toulouse, UPS, LCC, F-31077 Toulouse, France,2 Institut de Chimie des Substances Naturelles du CNRS, 91198 Gif-sur-Yvette Cedex, France3

Received 3 September 2008/ Returned for modification 1 October 2008/ Accepted 7 November 2008

Malaria is one of the most significant causes of infectious disease in the world. The search for new antimalarial chemotherapies has become increasingly urgent due to the parasites’ resistance to current drugs. Ellagic acid is a polyphenol found in various plant products. In this study, antimalarial properties of ellagic acid were explored. The results obtained have shown high activity in vitro against all Plasmodium falciparum strains whatever their levels of chloroquine and mefloquine resistance (50% inhibitory concentrations ranging from 105 to 330 nM). Ellagic acid was also active in vivo against Plamodium vinckei petteri in suppressive, curative, and prophylactic murine tests, without any toxicity (50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day). The study of the point of action of its antimalarial activity in the erythrocytic cycle of Plasmodium falciparum demonstrated that it occurred at the mature trophozoite and young schizont stages. Moreover, ellagic acid has been shown to potentiate the activity of current antimalarial drugs such as chloroquine, mefloquine, artesunate, and atovaquone. This study also proved the antioxidant activity of ellagic acid and, in contrast, the inhibitory effect of the antioxidant compound N-acetyl-L-cysteine on its antimalarial efficacy. The possible mechanisms of action of ellagic acid on P. falciparum are discussed in light of the results. Ellagic acid has in vivo activity against plasmodia, but modification of the compound could lead to improved pharmacological properties, principally for the oral route.

* Corresponding author. Mailing address: Service de Parasitologie, Toulouse Hospital University, 1 Av. Poulhès, TSA50032, 31059 Toulouse Cedex 9, France. Phone: 33 561323446. Fax: 33 561322096. E-mail: Francoise.Vical{at}inserm.fr

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, March 2009, p. 1100-1106, Vol. 53, No. 3
0066-4804/09/$08.00+0     doi:10.1128/AAC.01175-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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