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Antimicrobial Agents and Chemotherapy, January 2004, p. 130-136, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.130-136.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro and In Vivo Activities of a Triterpenoid Saponin Extract (PX-6518) from the Plant Maesa balansae against Visceral Leishmania Species

Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp,¹ Tibotec NV, Mechelen,² Department of Organic Chemistry, Ghent University, Ghent, Belgium,⁴ National Center for Natural Sciences and Technology, Cau Giay District, Hanoi, Vietnam³

Received 10 July 2003/ Returned for modification 16 July 2003/ Accepted 22 September 2003

The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC₅₀) against intracellular Leishmania infantum amastigotes was 0.04 µg/ml. The cytotoxic concentrations causing 50% cell death (CC₅₀s) were about 1 µg/ml in murine macrophage host cells and >32 µg/ml in human fibroblasts (MRC-5 cell line). Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver amastigote burdens by about 95% in all treated animals. If treatment was delayed until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to maintain the same level of activity. Single 250-mg/kg doses of sodium stibogluconate (Pentostam) 1 and 14 days after infection produced comparable efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before infection was still 100% effective in preventing liver infection, suggesting a particularly long residual action. Spleen and bone marrow could not be cleared by PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid saponins from M. balansae show promising in vitro and in vivo antileishmanial potential and can be considered as new lead structures in the search for novel antileishmanial drugs.

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