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Antimicrobial Agents and Chemotherapy, March 2004, p. 924-929, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.924-929.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Maria Mamani-Matsuda,^1* Jérôme Rambert,¹ Denis Malvy,^1,2 Hélène Lejoly-Boisseau,¹ Sylvie Daulouède,¹ Denis Thiolat,¹ Sara Coves,³ Pierrette Courtois,¹ Philippe Vincendeau,¹ and M. Djavad Mossalayi¹

Laboratoires d'Immunologie et de Parasitologie, E.A. 3677, Bases Thérapeutiques Anti-Infectieuses et Anti-Inflammatoires, Université Bordeaux II,¹ Service de Médecine Interne et des Maladies Tropicales, Hôpital Saint André, Bordeaux,² Unilever France, Rueil-Malmaison, France³

Received 11 July 2003/ Returned for modification 13 October 2003/ Accepted 29 November 2003

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)- and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF- and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.

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* Corresponding author. Mailing address: Laboratoire d'Immunologie et de Parasitologie, Faculté de Pharmacie, Université Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. Phone: 33 5 57 57 12 43. Fax: 33 5 57 57 12 10. E-mail: maria.mamani{at}u-bordeaux2.fr.

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Antimicrobial Agents and Chemotherapy, March 2004, p. 924-929, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.924-929.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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