Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Mar;53(3):1100-6.
doi: 10.1128/AAC.01175-08. Epub 2008 Nov 17.

In vitro and in vivo properties of ellagic acid in malaria treatment

Patrice Njomnang Soh  1 , Benoît Witkowski, David Olagnier, Marie-Laure Nicolau, Maria-Concepcion Garcia-Alvarez, Antoine Berry, Françoise Benoit-Vical
Affiliations

In vitro and in vivo properties of ellagic acid in malaria treatment

Patrice Njomnang Soh et al. Antimicrob Agents Chemother. 2009 Mar.

Abstract

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.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Ellagic acid. The chemical formula is C14H6O8; the molecular weight is 302.197 g/mol.
FIG. 2.
FIG. 2.
Means of ellagic acid antiplasmodial activities in vitro against five Plasmodium falciparum strains according to data from at least three independent experiments for each strain.
FIG. 3.
FIG. 3.
Chloroquine resistance reversal by ellagic acid. Values correspond to the means of data from three independent experiments. (a) Mean of reversal concentration of verapamil (positive control) for chloroquine-resistant strain W2 (CR50 equal to 0.31 ± 0.07 μM). (b) Absence of reversion by ellagic acid for chloroquine-resistant strain W2. (c) Absence of reversion by ellagic acid for chloroquine-sensitive strain F32 (negative control).
FIG. 4.
FIG. 4.
Mefloquine resistance reversal by ellagic acid. Values are the means of three independent experiments. (a) Means of reversal concentrations of penfluridol (positive control) for mefloquine-resistant strain Dd2 (CR50 for penfluridol of 96 ± 7 ng/ml). (b) Means of reversal concentrations of ellagic acid for mefloquine-resistant strain Dd2 (CR50 for ellagic acid of 5 ± 4 ng/ml). (c) Absence of reversion by ellagic acid for mefloquine-sensitive strain FcM29 (negative control).
FIG. 5.
FIG. 5.
Point of action of ellagic acid on the erythrocytic life cycle.
FIG. 6.
FIG. 6.
Percentage of inhibition of parasite growth in vivo compared with that in untreated control mice versus dose of ellagic acid (or artesunate) at day 4 of treatment by the oral and intraperitoneal routes assessed by the 4-day suppressive test.
FIG. 7.
FIG. 7.
Percentages of inhibition of parasite growth in vivo and standard deviations at day 6 in all groups of mice infected with P. vinckei petteri and either orally (100 mg/kg/day) or intraperitoneally (10 mg/kg/day) treated by doses of ellagic acid compared with untreated controls. Day zero corresponds to the day of Plasmodium infection.
FIG. 8.
FIG. 8.
Inhibition effect of ellagic acid antiplasmodial activity by the antioxidant compound NAC on strain FcM29 of P. falciparum.
FIG. 9.
FIG. 9.
Antioxidant effect of ellagic acid on human monocytes using PMA, which induced a strong generation of ROS.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Arnot, D. E., and K. Gull. 1998. The Plasmodium cell-cycle: facts and questions. Ann. Trop. Med. Parasitol. 92:361-365. - PubMed
    1. Arreesrisom, P., A. M. Dondorp, S. Looareesuwan, and R. Udomsangpetch. 2007. Suppressive effects of the anti-oxidant N-acetylcysteine on the anti-malarial activity of artesunate. Parasitol. Int. 56:221-226. - PubMed
    1. Banzouzi, J. T., R. Prado, H. Menan, A. Valentin, C. Roumestan, M. Mallie, Y. Pelissier, and Y. Blache. 2002. In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid. J. Ethnopharmacol. 81:399-401. - PubMed
    1. Benoit, F., A. Valentin, Y. Pelissier, F. Diafouka, C. Marion, D. Kone-Bamba, M. Kone, M. Mallie, A. Yapo, and J. M. Bastide. 1996. In vitro antimalarial activity of vegetal extracts used in West African traditional medicine. Am. J. Trop. Med. Hyg. 54:67-71. - PubMed
    1. Benoit-Vical, F. 2005. Ethnomedicine in malaria treatment. IDrugs 8:45-52. - PubMed

Publication types

MeSH terms

LinkOut - more resources