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JAC Advance Access published online on June 10, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn223
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Anti-Trichomonas activity of Sapindus saponins, a candidate for development as microbicidal contraceptive

Pratibha Tiwari{dagger}, Divya Singh{dagger} and Man Mohan Singh*,{dagger}

Division of Endocrinology, Central Drug Research Institute, Lucknow 226 001, India

Received 22 February 2008; returned 31 March 2008; revised 30 April 2008; accepted 12 May 2008

* Corresponding author. Tel: +91-522-2612411-18, ext. 4307; Fax: +91-522-2623405; E-mail: singhmm{at}rediffmail.com

Objectives: Trichomoniasis is the most common non-viral sexually transmitted disease and is caused by the protozoan Trichomonas vaginalis. In view of increased resistance of the parasite to classical drugs of the metronidazole family, the need for new unrelated agents is increasing. This study evaluates anti-Trichomonas activity of Sapindus saponins, a component of a herbal local contraceptive Consap recently marketed in India.

Methods: The parasites were treated with saponins for MIC determination. Anti-Trichomonas activity of the saponins was evaluated using a cytoadherence assay, the substrate gel electrophoresis method and RT–PCR analysis. The effect of saponins on the mitochondrial potential of the host was determined by florescence-activated cell sorter. Actin cytoskeletal staining was used to determine the effect on parasite cytoskeleton.

Results: Using in vitro susceptibility assay, the MIC of Sapindus saponins for T. vaginalis (0.005%) was found to be 10-fold lower than its effective spermicidal concentration (0.05%). Saponins concentration dependently inhibited the ability of parasites to adhere to HeLa cells and decreased proteolytic activity of the parasite’s cysteine proteinases. This was associated with decreased expression of adhesin AP65 and membrane-expressed cysteine proteinase TvCP2 genes. Saponins produced no adverse effect on host cells in mitochondrial reduction potential measurement assay. Saponins also reversed the inhibitory mechanisms exerted by Trichomonas for evading host immunity. Early response of saponins to disrupt actin cytoskeleton in comparison with their effect on the nucleus suggests a membrane-mediated mode of action rather than via induction of apoptosis.

Conclusions: Findings demonstrate the potential of Sapindus saponins for development as a microbicidal contraceptive for human use. Further studies are required to evaluate its microbicidal activity against other sexually transmitted infections.

Key Words: susceptibility , cytoadherence , adhesin , Consap

{dagger} The authors have contributed equally.


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