J Med Microbiol Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dutta, A.
Right arrow Articles by Mandal, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dutta, A.
Right arrow Articles by Mandal, C.
Agricola
Right arrow Articles by Dutta, A.
Right arrow Articles by Mandal, C.
J Med Microbiol 56 (2007), 1196-1204; DOI: 10.1099/jmm.0.47114-0
© 2007 Society for General Microbiology
ISSN 1473-5644

Racemoside A, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in Leishmania donovani

Avijit Dutta1, Angana Ghoshal1, Debayan Mandal2, Nirup B. Mondal2, Sukdeb Banerjee2, Niranjan P. Sahu2 and Chitra Mandal1

1 Department of Infectious Disease and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India

2 Steroid and Terpenoid Chemistry, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India

Correspondence
Chitra Mandal
cmandal{at}iicb.res.in

Received 8 December 2006
Accepted 7 May 2007

Leishmaniasis remains a major health problem of the tropical and subtropical world. The visceral form causes the most fatalities if left untreated. Dramatic increases in the rates of infection and drug resistance and the non-availability of safe vaccines have highlighted the need for identification of novel and inexpensive anti-leishmanial agents. This study reports that racemoside A, a water-soluble steroidal saponin purified from the fruits of Asparagus racemosus, is a potent anti-leishmanial molecule effective against antimonial-sensitive (strain AG83) and -unresponsive (strain GE1F8R) Leishmania donovani promastigotes, with IC50 values of 1.15 and 1.31 µg ml–1, respectively. Incubation of promastigotes with racemoside A caused morphological alterations including cell shrinkage, an aflagellated ovoid shape and chromatin condensation. This compound exerts its leishmanicidal effect through the induction of programmed cell death mediated by the loss of plasma membrane integrity as detected by binding of annexin V and propidium iodide, loss of mitochondrial membrane potential culminating in cell-cycle arrest at the sub-G0/G1 phase, and DNA nicking shown by deoxynucleotidyltransferase-mediated dUTP end labelling (TUNEL). Racemoside A also showed significant activity against intracellular amastigotes of AG83 and GE1F8R at a 7–8-fold lower dose, with IC50 values of 0.17 and 0.16 µg ml–1, respectively, and was non-toxic to murine peritoneal macrophages up to a concentration of 10 µg ml–1. Hence, racemoside A is a potent anti-leishmanial agent that merits further pharmacological investigation.

Abbreviations: MFI, mean fluorescence intensity; PCD, programmed cell death; PI, propidium iodide; SAG, sodium antimony gluconate; TdT, terminal deoxynucleotidyltransferase; TUNEL, TdT-mediated dUTP end labelling.




This article has been cited by other articles:


Home page
 Am J Trop Med HygHome page
H. Hillesland, A. Read, B. Subhadra, I. Hurwitz, R. McKelvey, K. Ghosh, P. Das, and R. Durvasula
Identification of Aerobic Gut Bacteria from the Kala Azar Vector, Phlebotomus argentipes: A Platform for Potential Paratransgenic Manipulation of Sand Flies
Am J Trop Med Hyg, December 1, 2008; 79(6): 881 - 886.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
INT J SYST EVOL MICROBIOL J MED MICROBIOL MICROBIOLOGY J GEN VIROL ALL SGM JOURNALS
Copyright © 2007 Society for General Microbiology.