Quassinoid constituents of Quassia amara L. leaf herbal tea. Impact on its antimalarial activity and cytotoxicity
Graphical abstract
Introduction
Within the framework of a study aiming at identifying traditional antimalarial remedies, we have had the opportunity of working in French Guiana. In this French department, the incidence of malaria is very high (one of the highest in South-America) (Chaud et al., 2006). Further to a knowledge attitudes and practices study conducted in that country, we have identified certain remedies used commonly by the population for curing or diminishing the symptoms of malaria crises (Bertani et al., 2005, Vigneron et al., 2005). Among the remedies listed, one is used predominantly. It consists of a prolonged decoction of mature leaves of Quassia amara L. (Simaroubaceae), administered orally. The antimalarial activity of this preparation was assessed in vitro and in vivo (Bertani et al., 2005, Bertani et al., 2006) and in order to optimize the in vitro antimalarial activity, later on, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of leaves collected at the apex, hence young leaves, and prepared when fresh, i.e., without any prior desiccation. This preparation demonstrated a very good activity, in vitro as well as in vivo (Bertani et al., 2007). An active compound, simalikalactone D (SkD), could be identified within this preparation (Bertani et al., 2006). SkD is a quassinoid with exceptional in vitro activity against Plasmodium falciparum (IC50 = 10 nM). However, it is also cytotoxic for a number of cellular lineages (see for example Ozeki et al., 1998, Xu et al., 2000). We then deemed significant to be able to characterize, quantify, assess the antiparasitic and cytotoxic activities of all the quassinoids present in the herbal tea prepared with young leaves of Q. amara, and to compare antimalarial activity and cytotoxicity (or presumed toxicity) of this preparation. In fine, our objective was to assess whether it could be contemplated to recommend this preparation for treatment against malaria, and if yes, set up a standard protocol for preparing the herbal tea in order to guarantee a constant amount of active principle administered.
Section snippets
General remarks
Dichloromethane (laboratory grade) was purchased from Fisher Scientific, acetonitrile (Lichrosolv grade) was purchased from Merck. Water (HPLC grade) was obtained from a Milli-Q system (Mili-Q plus, Millipore Bedford, MA). Other reagents were purchased from Sigma–Aldrich unless otherwise stated.
Semi-preparative chromatography was performed with a W600 pump and a W2996 photodiode array absorbance detector (Waters®) using a Discovery® C18 column (25 cm × 21.2 mm, 5 μm, Supelco®).
Optical rotations were
Results and discussion
Seven quassinoids have been isolated and characterized in the herbal tea made with young fresh leaves. These are simalikalactone D (SkD, 1), picrasin B (2), picrasin H (2-O-methylpicrasin B, 3), neoquassin (4), quassin (5), picrasin I (6) and picrasin J (7) (Fig. 1).
In addition to SkD (1), picrasin B (2), quassin (5) and neoquassin (4) have already been isolated from natural sources (see for example Valenta et al., 1961, Hikino et al., 1975, Apers et al., 2002). Picrasin H (3) has already been
Conclusions
To conclude, an in-depth study of the composition of a Q. amara herbal tea prepared from young and fresh leaves for optimizing its antimalarial activity has enabled us to isolate and to characterize six quassinoids other than SkD. Two of these molecules are new, and one is described for the first time as a natural product. None of these quassinoids has a significant activity on in vitro culture of P. falciparum or on cellular lineage in mammals. The activity of this herbal tea hence appears
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