Phytochemical Profile and Biological Activity Evaluation of Zanthoxylum heterophyllum Leaves against Malaria

Abstract

!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...

The potential of anti-malarial compounds derived from African medicinal plants: a review of pharmacological evaluations from 2013 to 2019

“…The amide hydroxyγ-isosanshool (174) and the coumarin bergenin (175), Fig. 37, obtained from the leaves of Zanthoxylum heterophyllum (Rutaceae) and Diospyros conocarpa (Ebenaceae), respectively [107,108]. While the amide showed and activity against the 3D7 strain with IC 50 = 39.04 µM [107], and percentage viability of compound 175 was recorded as 101.15 against the same plasmodial strain [108].…”

“…37, obtained from the leaves of Zanthoxylum heterophyllum (Rutaceae) and Diospyros conocarpa (Ebenaceae), respectively [107,108]. While the amide showed and activity against the 3D7 strain with IC 50 = 39.04 µM [107], and percentage viability of compound 175 was recorded as 101.15 against the same plasmodial strain [108]. Lenta et al also isolated three known coumarins; canaliculatin (176), plumbagin (177) and ismailin (178) from the stem bark of Diospyros canaliculata (Ebenaceae) harvested from Cameroon [90].…”

Antiplasmodial, anti-chikungunya virus and antioxidant activities of 64 endemic plants from the Mascarene Islands

“…As far as we know, these 3 plants have never been either phytochemically nor pharmacology studied. Our team further investigated these plants and discovered that hydroxy-γ-isosanshool was the main active compound of the extract of Z. heterophyllum, with IC 50 corresponding to 11.3 ± 1.5 µg/mL (Ledoux et al, 2015) and Poupartones A, B and C (alkylphenol cyclohexenones derivatives, with IC 50 < 1 µg/mL) in P. borbonica, the main antiplasmodial compounds in our in vitro and in vivo assays (Ledoux et al, 2017). The use of Zanthoxylum heterophyllum in decoction to treat fever in traditional medicine [20] may be correlated with its antiplasmodial properties.…”

Identification of the candidate genes related to sanshool biosynthesis in Zanthoxylum bungeanum by comparative RNA sequencing analysis

“…Zanthoxylum bungeanum, usually called Sichuan pepper or Chinese red pepper, is one of the most representative species of Zanthoxylum in China and is mainly used as a spice in Chinese cuisine and in traditional herbal medicine for the treatment of stomachache, toothache, diarrhoea, ascariosis, and colic. Like other species in the Zanthoxylum genus, such as Z. piperitum 2 , Z. heterophyllum 3 and Z. armatum 4 , the most valuable tissue of Z. bungeanum is the pericarp which is rich in a number of bioactive secondary metabolites, including coumarins, aromatic and aliphatic amides, alkaloids and lignans. Among these metabolites, aliphatic amides, which are classified as sanshools, are the major active components.…”