Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis

Mittra, Bidyottam ; Saha, Asim ; Roy Chowdhury, Arnab ; Pal, Chiranjib ; Mandal, Suparna ; Mukhopadhyay, Sibabrata ; Bandyopadhyay, Santu ; Majumder, Hemanta K. (2000) Luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase II-mediated kinetoplast DNA cleavage leading to apoptosis Molecular Medicine, 6 (6). pp. 527-541. ISSN 1076-1551

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Official URL: http://www.molmed.org/content/2000/527.pdf

Abstract

Background: Plant-derived flavonoids, which occur abundantly in our daily dietary intake, possess antitumor, antibacterial, and free radical scavenging properties. They form active constituents of a number of herbal and traditional medicines. Several flavonoids have been shown to exert their action by interacting with DNA topoisomerases and promoting site-specific DNA cleavage. Therefore, flavonoids are potential candidates in drug design. We report here that, although the flavonoids luteolin and quercetin are potent antileishmanial agents, luteolin has great promise for acting as a lead compound in the chemotherapy of leishmaniasis, a major concern in developing countries. Materials and Methods: Kinetoplast DNA (kDNA) minicircle cleavage in drug-treated parasites was measured by electrophoresis of the total cellular DNA, followed by Southern hybridization using 32P labeled kDNA as a probe. Cell cycle progression and apoptosis were measured by flow cytometry using propidium iodide and fluorescein isothiocyanate (FITC)- labeled Annexin V. Results: Luteolin and quercetin inhibited the growth of Leishmania donovani promastigotes and amastigotes in vitro, inhibited DNA synthesis in promastigotes, and promoted topoisomerase-IImediated linearization of kDNA minicircles. The IC50 values of luteolin and quercetin were 12.5 μ M and 45.5 μ M, respectively. These compounds arrest cell cycle progression in L. donovani promastigotes, leading to apoptosis. Luteolin has no effect on normal human T-cell blasts. Both luteolin and quercetin reduced splenic parasite burden in animal models. Conclusion: Luteolin and quercetin are effective antileishmanial agents. Quercetin has nonspecific effects on normal human T cells, but luteolin appears nontoxic. So, luteolin can be a strong candidate for antileishmanial drug design.

Item Type:Article
Source:Copyright of this article belongs to The Feinstein Institute for Medical Research.
ID Code:72071
Deposited On:28 Nov 2011 05:31
Last Modified:28 Nov 2011 05:31

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