Racemoside A, An Anti-leishmanial, Water-Soluble, Natural Steroidal Saponin, Induces Programmed Cell Death in Leishmania donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, KolkataView Archive Info
Racemoside A, An Anti-leishmanial, Water-Soluble,
Natural Steroidal Saponin, Induces Programmed Cell
Death in Leishmania donovani
Mondal, Nirup B
Sahu, Niranjan P
Infectious Diseases and Immunology
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 mg 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 mgml”1, respectively, and was non-toxic to murine peritoneal macrophages up to a concentration of 10 mg ml”1. Hence, racemoside A is a potent anti-leishmanial agent that merits further pharmacological investigation.
Dutta, Avijit and Ghoshal, Angana and Mandal, Debayan and Mondal, Nirup B and Banerjee, Sukdeb and Sahu, Niranjan P and Mandal, Chitra (2007) Racemoside A, An Anti-leishmanial, Water-Soluble, Natural Steroidal Saponin, Induces Programmed Cell Death in Leishmania donovani. Journal of Medical Microbiology, 56 (9). pp. 1196-1204.