Document Detail


Racemoside A, an anti-leishmanial, water-soluble, natural steroidal saponin, induces programmed cell death in Leishmania donovani.
MedLine Citation:
PMID:  17761483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 IC(50) values of 1.15 and 1.31 microg 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-G(0)/G(1) 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 IC(50) values of 0.17 and 0.16 microg ml(-1), respectively, and was non-toxic to murine peritoneal macrophages up to a concentration of 10 microg ml(-1). Hence, racemoside A is a potent anti-leishmanial agent that merits further pharmacological investigation.
Authors:
Avijit Dutta; Angana Ghoshal; Debayan Mandal; Nirup B Mondal; Sukdeb Banerjee; Niranjan P Sahu; Chitra Mandal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medical microbiology     Volume:  56     ISSN:  0022-2615     ISO Abbreviation:  J. Med. Microbiol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-31     Completed Date:  2007-10-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0224131     Medline TA:  J Med Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1196-204     Citation Subset:  IM    
Affiliation:
Department of Infectious Disease and Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Annexin A5 / metabolism
Antiprotozoal Agents / pharmacology*,  toxicity
Apoptosis*
Asparagus Plant / chemistry
Cell Membrane Permeability / drug effects
Cell Survival
Cells, Cultured
DNA Breaks, Single-Stranded
In Situ Nick-End Labeling
Inhibitory Concentration 50
Leishmania donovani / cytology,  drug effects*
Macrophages, Peritoneal / drug effects
Membrane Potential, Mitochondrial / drug effects
Mice
Mice, Inbred BALB C
Plant Extracts / pharmacology
Propidium / metabolism
Saponins / isolation & purification,  pharmacology*
Steroids / isolation & purification,  pharmacology*
Chemical
Reg. No./Substance:
0/Annexin A5; 0/Antiprotozoal Agents; 0/Plant Extracts; 0/Saponins; 0/Steroids; 36015-30-2/Propidium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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