Zanthoxylum chiloperone leaves extract: First sustainable Chagas disease treatment

• Published in: Journal of ethnopharmacology 2011-02, Vol.133 (3), p.986-993
• Main Authors: Ferreira, Maria Elena, Cebrián-Torrejón, Gerardo, Corrales, Alba Segovia, Vera de Bilbao, Ninfa, Rolón, Miriam, Gomez, Celeste Vega, Leblanc, Karine, Yaluf, Gloria, Schinini, Alicia, Torres, Susana, Serna, Elva, Rojas de Arias, Antonieta, Poupon, Erwan, Fournet, Alain
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Canthin-6-one; Chagas disease; Chagas Disease - drug therapy; Chromatography, High Pressure Liquid; Cytotoxicity; Experimental treatment; Female; General pharmacology; HPLC–UV–MS; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Medical sciences; Mice; Mice, Inbred BALB C; Mutagenicity; Mutagenicity Tests; Paraguay; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Plant Leaves - chemistry; Rutaceae; Spectrophotometry, Ultraviolet; Trypanosoma cruzi; Zanthoxylum; Zanthoxylum - chemistry; Zanthoxylum chiloperone
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2010.11.032

HPLC–UV–MS chromatogram of ethanolic extracts of Zanthoxylum chiloperone and effects on parasitaemia in BALB/c mice with acute Trypanosoma cruzi infection by Y strain (% mortality). Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) stem bark is used traditionally in Paraguay for its antiparasitic properties. Canthin-6-one is main compound isolated from Zanthoxylum chiloperone var angustifolium with broad spectrum antifungal, leishmanicidal and trypanocidal activities. The qualitative and quantitative characterization and the isolation of main alkaloidal components of different organs of Zanthoxylum chiloperone are investigated by HPLC–UV–MS. The in vitro biological activity of each extract against trypomastigote and amastigote forms of Trypanosoma cruzi parasites were evaluated, then comparison the in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone with reference drug, benznidazole, in acute Trypanosoma cruzi infected mice when administered by oral route. We have also evaluated the mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, i.e. canthin-6-one, by mouse bone marrow micronucleus test. The compositions of the ethanol extracts obtained after the maceration process were studied by HPLC–UV–MS methods. The quantitation analysis was performed by external standard method, using a calibration curve constructed utilizing solutions containing different concentrations of the reference samples. The anti-trypomastigote activity was evaluated by the lysis effect on mouse blood trypomastigotes (Y strain Trypanosoma cruzi). The anti-amastigote Trypanosoma cruzi activity was evaluated by a modified colorimetric method with chlorophenol red-β-d-galactopyranoside (CPRG). The cytotoxicity of extracts and compounds was performed on NCTC 929 cells. The in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone and benznidazole, in acute Trypanosoma cruzi (two different strains) was evaluated in Trypanosoma cruzi infected mice; the drugs were administered by oral route. The mortality rates were recorded and parasitaemias in control and treated mice were determined once weekly for 70 days. The mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, canthin-6-one, by mouse bone marrow micronucleus test. Canthin-6-one was the main compound of stem and root bark and 5-methoxy-canthin-6-one in leaves and fruits. The ethanolic leaves extract, canthin-6-one and benznidaz