Planta Med 2007; 73 - P_135
DOI: 10.1055/s-2007-986916

Modulation of the in vitro antimalarial effects of artemisinin by selected flavonoids and by reducing agents

AR Sannella 1, L Messori 2, A Casini 2, FF Vincieri 3, G Maiori 1, C Severini 1, AR Bilia 3
  • 1Department of Infectious, Parasitic and Immunomediated Diseases, Vector-Borne Diseases and International Health Section, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy
  • 2Department of Chemistry, University of Florence, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Florence, Italy
  • 3Department of Pharmaceutical Sciences, University of Florence, Via U. Schiff 6,50019 Sesto Fiorentino, Florence, Italy

Within the framework of a larger research project [1] aimed at evaluating the possible synergistic effects in malaria treatment between artemisinin and a variety of natural substances commonly present in plant extracts, the specific antiplasmodial properties of some flavonoids (catechin, epicatechin, quercetin, rutin, eryodictiol and eriodictyol chalcone) and of two reducing agents (ascorbic acid and ascorbyl octanoate) in combination with artemisinin were evaluted against 3D7 P. falciparum strains in vitro.

The possible synergism between artemisinin and the single constituents on the parasite growth was investigated adding artemisinin at sublethal doses ranging from 0.625 to 20 nM, in presence or absence) of 10µM or 1 mM concentrations of the individual compounds. The effect of artemisinin tested at different concentrations and 10µM quercetin are more than additive, and this effect greatly increased when quercetin was tested at 1mM concentrations, implying a moderate synergism between these two substances. The other flavonoids did not show any significant synergistic activity. Ascorbic acid did not show any synergistic effect while ascorbyl octanoate tested at 1mM concentrations either alone or in combination with artemisinin determined a dramatic increase of the parasitemia. The observed synergism between quercetin and artemisinin might be conveniently exploited to design new and/or more effective combination therapies.

Acknowledgments: The Ente Cassa di Risparmio di Firenze is gratefully acknowleged for generous financial support.

References: [1] Sannella, A.R. et al. (2007) Biochem Biophys Res Commun 353: 177–181.