!The aim of this study was to evaluate the antiplasmodial properties of Zanthoxylum heterophyllum, an endemic plant from the Mascarene Islands. In vitro antiplasmodial activity of ethyl acetate and dichloromethane crude extracts obtained from leaf samples collected on Reunion Island was evaluated on the Plasmodium falciparum 3D7 chloroquine-sensitive strain using a colorimetric method. The major active compound was identified by chromatographic and spectroscopic methods. The best antiplasmodial activity was obtained for the ethyl acetate extract (15 µg/ mL < IC 50 < 50 µg/mL). The major compound was identified as a sanshool derivative, an alkylamide compound that has moderate antimalarial activity (IC 50 = 11.3 µg/mL). This is the first report of the presence of a sanshool derivative in Z. heterophyllum. The moderate antiplasmodial activity of hydroxy-γ-isosanshool was demonstrated for the first time. Key wordsZanthoxylum heterophyllum · Rutaceae · malaria · antiplasmodial activitiy · Réunion Island · sanshool Supporting information available online at http://www.thieme-connect.de/products According to the last World Malaria Report [1], there were an estimated 627 000 malaria deaths worldwide in 2012. Malaria is caused by a parasite Plasmodium sp. and transmitted by Anopheles mosquitoes. The problem of parasite resistance towards available medicines such as chloroquine is increasing. Natural products could play an important role in the discovery of new antimalarial drugs. Indeed, the vegetal kingdom is an important source of new pharmacological active compounds, especially for the search of new antimalarial drugs as reviewed by Bero and al. [2]. Zanthoxylum heterophyllum Sm. is an endemic plant from Reunion Island, which belongs to the Rutaceae family [3]. In the traditional pharmacopoeia of the island, Z. heterophyllum, commonly named "poivrier des hauts", is used for the treatment of backaches [4]. As far as we know, pharmacological properties of this plant have not been studied before, except in a paper where methanol leaf and stem extracts showed free radical scavenging properties [5]. Nevertheless, some Zanthoxylum species are known to have antiplasmodial properties, such as Zanthoxylum chalybeum [6] and Zanthoxylum zanthoxyloides [7]. Results and Discussion !The major compound present in the ethyl acetate crude extract was identified as a sanshool derivative. Some sanshool derivates were already described in Zanthoxylum sp., such as Z.anthoxylum piperitum [8] and Z.anthoxylum integrifoliolum [9]. By comparison of our NMR and MS data with literature data, it was identified as hydroxy-γ-isosanshool (l " Fig. 1), described by Chen et al. [9]. Ethyl acetate and dichloromethane crude extracts and hydroxy-γ-isosanshool (purity 90.58 %) were tested in vitro against the Plasmodium falciparum 3D7 strain. In line with WHO guidelines and previous results from our team (Jansen et al. [10], Jonville et al. [11]), antiplasmodial crude extract activity was classified as follows: IC 50 ≤ 15 µg/mL, promising activ...
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