Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages.
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)-alpha 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-alpha 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.
Mamani-Matsuda
Maria
M
Laboratoires d'Immunologie et de Parasitologie, E.A. 3677, Bases Thérapeutiques Anti-Infectieuses et Anti-Inflammatoires, Université Bordeaux II, France. maria.mamani@u-bordeaux2.fr
Rambert
Jérôme
J
Malvy
Denis
D
Lejoly-Boisseau
Hélène
H
Daulouède
Sylvie
S
Thiolat
Denis
D
Coves
Sara
S
Courtois
Pierrette
P
Vincendeau
Philippe
P
Mossalayi
M Djavad
MD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007249:Inflammation / Q000378:metabolism*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D011794:Quercetin / Q000494:pharmacology*; D014347:Trypanosoma brucei gambiense / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007202:Indicators and Reagents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011794:Quercetin