Effect of Apigenin on Leishmania amazonensis Is Associated with Reactive Oxygen Species Production Followed by Mitochondrial Dysfunction

Journal of Natural Products
Fernanda Fonseca-SilvaElmo E Almeida-Amaral

Abstract

Leishmaniasis is an important neglected disease caused by protozoa of the genus Leishmania that affects more than 12 million people worldwide. Leishmaniasis treatment requires the administration of toxic and poorly tolerated drugs, and parasite resistance greatly reduces the efficacy of conventional medications. Apigenin (1), a naturally occurring plant flavone, has a wide range of reported biological effects. In this study, antileishmanial activity of 1 in vitro was investigated, and its mechanism of action against Leishmania amazonensis promastigotes was described. Treatment with 1 for 24 h resulted in concentration-dependent inhibition of cellular proliferation (IC50 = 23.7 μM) and increased reactive oxygen species (ROS) generation. Glutathione and N-acetyl-l-cysteine protected L. amazonensis from the effects of 1 and reduced ROS levels after the treatment. By contrast, oxidized glutathione did not reduce the levels of ROS caused by 1 by not preventing the proliferation inhibition. Apigenin 1 also induced an extensive swelling in parasite mitochondria, leading to an alteration of the mitochondrial membrane potential, rupture of the trans-Golgi network, and cytoplasmic vacuolization. These results demonstrate the leishmanicid...Continue Reading

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Citations

Jan 15, 2016·Micron : the International Research and Review Journal for Microscopy·B J M Da SilvaE O Silva
Jan 23, 2016·Experimental Parasitology·Simone Carolina Soares Petri e SilvaJosé Angelo Lauletta Lindoso
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