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Luteolin, an Abundant Dietary Component is a Potent Anti-leishmanial Agent that Acts by Inducing Topoisomerase II-mediated Kinetoplast DNA Cleavage Leading to Apoptosis

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Title Luteolin, an Abundant Dietary Component is a Potent Anti-leishmanial Agent that Acts by Inducing Topoisomerase II-mediated Kinetoplast DNA Cleavage Leading to Apoptosis
 
Creator Mittra, Bidyottam
Saha, Asim
Roy Chowdhury, Arnab
Pal, Chiranjib
Mandal, Suparna
Mukhopadhyay, Sibabrata
Bandyopadhyay, Santu
Majumder, Hemanta K
 
Subject Chemistry
Infectious Diseases and Immunology
 
Description 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 �M
and 45.5 �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.
 
Date 2000
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1630/1/Molecular_Medicine%2C_2000.pdf
Mittra, Bidyottam and Saha, Asim and Roy Chowdhury, Arnab and Pal, Chiranjib and Mandal, Suparna and Mukhopadhyay, Sibabrata and Bandyopadhyay, Santu and 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 Medicin, 6 (6). pp. 527-541.
 
Relation http://dx.doi.org/
http://www.eprints.iicb.res.in/1630/