Renaissance remedies: Antiplasmodial protostane triterpenoids from Alisma plantago-aquatica L. (Alismataceae)

Aim of the study: In a preliminary screen of extracts from plants used as antimalarial remedies used in Europe in the 16th and 17th, the ethyl acetate extract of Alisma plantago-aquatica L. (Alismataceae) was active against Plasmodium falciparum K1 strain with 77% growth inhibition at 4.91 mu g/ml. The aim of this study was to isolate and identify the substances responsible for this antiplasmodial activity. Materials and methods: With HPLC-based activity profiling in combination with HPLC hyphenated methods (HPLC-PDA,-MSn, HR-MS, and off-line microprobe NMR) the activity was assigned to time windows, and the substances contained therein were characterised chemically. The active compounds were isolated with semi-preparative HPLC and structures were elucidated with high resolution mass spectrometry, and 1D and 2D NMR spectroscopy. Results: Four compounds were isolated and identified as protostane triterpenoids alisol A, alisol B 11-monoacetate, alisol B 23-monoacetate, and alisol G. Their IC(50)s against Plasmodium falciparum ranged from 5.4 to 13.8 mu M. Conclusions: This is the first report of antiplasmodial activity from protostanes triterpenoids, and the first result of our ongoing project of screening for antiprotozoal natural products from remedies used in European renaissance medicine. (C) 2011 Elsevier Ireland Ltd. All rights reserved.