In vitro and in vivo activities of a triterpenoid saponin extract (PX-6518) from the plant Maesa balansae against visceral leishmania species.
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 (IC(50)) against intracellular Leishmania infantum amastigotes was 0.04 micro g/ml. The cytotoxic concentrations causing 50% cell death (CC(50)s) were about 1 micro g/ml in murine macrophage host cells and >32 micro g/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.
Maes
Louis
L
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium. louis.maes@ua.ac.be
Vanden Berghe
Dirk
D
Germonprez
Nils
N
Quirijnen
Ludo
L
Cos
Paul
P
De Kimpe
Norbert
N
Van Puyvelde
Luc
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D000432:Methanol; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal; D012503:Saponins / Q000494:pharmacology*; D012997:Solvents; D014744:Vietnam
D000972:Antineoplastic Agents, Phytogenic; D000981:Antiprotozoal Agents; D010455:Peptides; D010936:Plant Extracts; D012503:Saponins; D012997:Solvents; C481666:poly(arginyl-histidine); D000432:Methanol