The antiplasmodium effects of a traditional South American remedy: Zanthoxylum chiloperone var. angustifolium against chloroquine resistant and chloroquine sensitive strains of Plasmodium falciparum

Abstract

Zanthoxylum chiloperone var. angustifolium Engl., Rutaceae, is used in traditional medicine to treat fungal and protozoal infections in the central area of South America. Considering the increasing resistance of Plasmodium falciparum in malarial ridden areas, we explored the anti-plasmodial effects of three compounds isolated from Z. chiloperone. The pyranocoumarin transavicennol and the canthinone alkaloids, canthin-6-one and 5-methoxycanthin-6-one, were found to have IC50 on chloroquine/mefloquine resistant and sensitive strains of P. falciparum of 0.5-2.7, 2.0-5.3 and 5.1-10.4 μg/mL, respectively. Moreover, the formation of heme adducts by these compounds is described by a novel alternative method based on MS-CID methods. The alkylamide sanshool was also identified, for first time in this plant, in the dichloromethanic and ethanolic extracts and the extracts were found to be notably non-toxic and displayed good anti-plasmodial effects.

Antimalarial Activity of Plant Metabolites

“…The roots and stem barks of Zanthoxylum chiloperone have been used as a folk medicine for the treatment of malaria and for its emmenagogue and antirheumatic properties. The pyranocoumarin transavicennol (134) and two canthinone alkaloids, canthin-6-one (135) and 5-methoxycanthin-6-one (136), were identified from the stem barks of this plant by Cebriá n-Torrejón et al [66] (Figure 30). These compounds possessed antiplasmodial IC50 values against chloroquine/mefloquine resistant and sensitive strains of P. falciparum (F32,…”

Natural Phenolic Compounds and Derivatives as Potential Antimalarial Agents

“…Traditional medicine is still recurrently used to treat many infectious diseases [6,7]. The availability, low cost, and traditional knowledge that conveys trust in its efficiency are factors that sway populations to rely deeply on plants [8]. Ethnopharmacology has allowed the combination of both traditional and modern pharmaceutical approaches in order to discover novel compounds and screen them for diverse activities [7,8].…”

“…The availability, low cost, and traditional knowledge that conveys trust in its efficiency are factors that sway populations to rely deeply on plants [8]. Ethnopharmacology has allowed the combination of both traditional and modern pharmaceutical approaches in order to discover novel compounds and screen them for diverse activities [7,8]. Particularly in malaria, a great number of decoctions, teas, and other preparations from plants are traditionally used across different endemic countries [6,7].…”

“…It is difficult to find highly active antiplasmodial compounds within this class, and there is evidence of a great distinction between sensitive and resistant strains, as evidenced in ▶ Table 2. However, coumarins have been identified as the active components in some plants used traditionally against malaria [8,51]. ND: not determined Compound (7) was identified in the rhizome parts of Angelica purpuraefolia Chung, a Korean plant used in folk medicine, after extract tests revealed antiplasmodial activity [52].…”

“…Compound (8) was isolated and identified from Phyllanthus niruri L., a plant widely distributed in Indonesia with traditional application in malaria [51]. In vitro in the FCR-3 multidrug-sensitive strain, the activity was barely within the interesting range in discussion (< 2 µM), and unfortunately, no toxicity tests were performed.…”