In Vitro and In Vivo Activity of Anogeissus leiocarpa Bark Extract and Isolated Metabolites against Toxoplasma gondii

Abstract

Toxoplasma gondii, belonging to the Apicomplexa phylum, is a cosmopolitan protozoan parasite that affects at least 30% of the worldʼs population. In West Africa, the leaves and bark of the tree species Anogeissus leiocarpa (DC.) Guill. & Perr. are used against zoonosis in traditional medicine and play a key role in controlling diseases induced by Apicomplexans such as malaria. In this study, extracts, fractions, and pure compounds obtained from an ethanol extract of the bark of A. leiocarpa were evaluated against T. gondii infection in vitro and in vivo. The crude bark extract showed significant activity on tachyzoites from the T. gondii RH strain (IC₅₀ = 59.30 µg/mL). The crude bark extract without tannins and pure trachelosperogenin E purified by centrifugal partition chromatography showed the highest activity (IC₅₀s = 12.83 and 26.63 µg/mL, respectively) with satisfying selectivity indexes of 9.61 and 9.75, respectively. The crude bark extract without tannins and pure trachelosperogenin E were able to significantly inhibit host cell invasion by the parasite in vitro, while the crude bark extract without tannins was able to increase mice survival in our murine model of chronic toxoplasmosis. These results provide new biological data for natural compounds that could enhance the current panoply of treatments against toxoplasmosis.

Key words

Toxoplasma gondii - Anogeissus leiocarpa - Combretaceae - centrifugal partition chromatography - natural products - chemosensitivity

• References

• 1 Deng Y, Wu T, Zhai SQ, Li CH. Recent progress on anti-Toxoplasma drugs discovery: Design, synthesis and screening. Eur J Med Chem 2019; 183: 111711
• 2 Weiss LM, Dubey JP. Toxoplasmosis: a history of clinical observations. Int J Parasitol 2009; 39: 895-901
• 3 Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995; 172: 1561-1566
• 4 Baatz H, Mirshahi A, Puchta J, Gümbel H, Hattenbach LO. Reactivation of toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient. Ocul Immunol Inflamm 2006; 14: 185-187
• 5 Dannemann B, McCutchan JA, Israelski D, Antoniskis D, Leport C, Luft B, Nussbaum J, Clumeck N, Morlat P, Chiu J, Vilde J-L, Orellana M, Feigal D, Bartok A, Heseltine P, Leedom J, Remington J. Treatment of toxoplasmic encephalitis in patients with AIDS. A randomized trial comparing pyrimethamine plus clindamycin to pyrimethamine plus sulfadiazine. The California Collaborative Treatment Group. Ann Intern Med 1992; 116: 33-43
• 6 Doliwa C, Escotte-Binet S, Aubert D, Velard F, Schmid A, Geers R, Villena I. Induction of sulfadiazine resistance in vitro in Toxoplasma gondii . Exp Parasitol 2013; 133: 131-136
• 7 Meneceur P, Bouldouyre MA, Aubert D, Villena I, Menotti J, Sauvage V, Garin JF, Derouin F. In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrimethamine, sulfadiazine, and atovaquone. Antimicrob Agents Chemother 2008; 52: 1269-1277
• 8 Mann A, Gbate M, Nda-Umar A. Medicinal and economic Plants of Nupeland. Bida, Nigeria: Jube Evans Books and Publications; 2003
• 9 Adamu HM, Abayeh OJ, Agho MO, Abdullahi AL, Uba A, Dukku HU, Wufem BM. An ethnobotanical survey of Bauchi State herbal plants and their antimicrobial activity. J Ethnopharmacol 2005; 99: 1-4
• 10 Gansané A, Sanon S, Ouattara LP, Traoré A, Hutter S, Ollivier E, Azas N, Traore AS, Guissou IP, Sirima SB, Nebié I. Antiplasmodial activity and toxicity of crude extracts from alternatives parts of plants widely used for the treatment of malaria in Burkina Faso: contribution for their preservation. Parasitol Res 2010; 106: 335-340
• 11 Okpekon T, Yolou S, Gleye C, Roblot F, Loiseau P, Bories C, Grellier P, Frappier F, Laurens A, Hocquemiller R. Antiparasitic activities of medicinal plants used in Ivory Coast. J Ethnopharmacol 2004; 90: 91-97
• 12 Hamzaoui M, Renault JH, Nuzillard JM, Reynaud R, Hubert J. Stepwise elution of a three-phase solvent system in centrifugal partition extraction: a new strategy for the fractionation and phytochemical screening of a crude bark extract. Phytochem Anal 2013; 24: 367-373
• 13 Hubert J, Nuzillard JM, Purson S, Hamzaoui M, Borie N, Reynaud R, Renault JH. Identification of natural metabolites in mixture: a pattern recognition strategy based on (13)C NMR. Anal Chem 2014; 86: 2955-2962
• 14 Berthod A, Ruiz-Angel MJ, Carda-Broch S. Elution-extrusion countercurrent chromatography. Use of the liquid nature of the stationary phase to extend the hydrophobicity window. Anal Chem 2003; 75: 5886-5894
• 15 Sato T. Spectral differentiation of 3,3′-di-O-methylellagic acid from 4,4′-di-O-methylellagic acid. Phytochemistry 1987; 26: 2124-2125
• 16 Serafin C, Nart V, Malheiros A, de Souza MM, Fischer L, Delle Monache G, Della Monache F, Cechinel Filho V. Bioactive phenolic compounds from aerial parts of Plinia glomerata . Z Naturforschung C J Biosci 2007; 62: 196-200
• 17 Kelava T, Ćavar I, Čulo F. Biological actions of drug solvents. Period Biol 2011; 113: 311-320
• 18 Kuete V, Dongmo Mafodong FL, Celik I, Fobofou SAT, Ndontsa BL, Karaosmanoğlu O, Weissjohann LA, Tane P, Koparal AT, Sivas H. In vitro cytotoxicity of compounds isolated from Desbordesia glaucescens against human carcinoma cell lines. South Afr J Bot 2017; 111: 37-43
• 19 Asres K, Bucar F, Knauder E, Yardley V, Kendrick H, Croft SL. In vitro antiprotozoal activity of extract and compounds from the stem bark of Combretum molle . Phytother Res 2001; 15: 613-617
• 20 Kumulungui SB, Ondo-azi SA, Mewono L, Otogo Nʼnang E, Akagah B, Fumoux F, Traoré A. In vitro behaviour of Plasmodium falciparum strains by alkaloids and tannins extracted from root of Mitragyna inermis, a medicinal plant. Int J Curr Pharm Res 2016; 8: 24-27
• 21 Soh PN, Witkowski B, Olagnier D, Nicolau ML, Garcia-Alvarez MC, Berry A, Benoit-Vical F. In vitro and in vivo properties of ellagic acid in malaria treatment. Antimicrob Agents Chemother 2009; 53: 1100-1106
• 22 Tasdemir D, Lack G, Brun R, Rüedi P, Scapozza L, Perozzo R. Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem 2006; 49: 3345-3353
• 23 Derouin F, Chastang C. In vitro effects of folate inhibitors on Toxoplasma gondii . Antimicrob Agents Chemother 1989; 33: 1753-1759
• 24 Spalenka J, Escotte-Binet S, Bakiri A, Hubert J, Renault JH, Velard F, Duchateau S, Aubert D, Huguenin A, Villena I. Discovery of new inhibitors of Toxoplasma gondii via the pathogen box. Antimicrob Agents Chemother 2018; 62: e01640-17
• 25 Boyom FF, Fokou PV, Tchokouaha LR, Spangenberg T, Mfopa AN, Kouipou RM, Mbouna CJ, Donfack VF, Zollo PH. Repurposing the open access malaria box to discover potent inhibitors of Toxoplasma gondii and Entamoeba histolytica . Antimicrob Agents Chemother 2014; 58: 5848-5854
• 26 DʼAngelo JG, Bordón C, Posner GH, Yolken R, Jones-Brando L. Artemisinin derivatives inhibit Toxoplasma gondii in vitro at multiple steps in the lytic cycle. J Antimicrob Chemother 2009; 63: 146-150
• 27 Robert-Gangneux F, Dardé ML. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 2012; 25: 264-296
• 28 De Craeye S, Speybroeck N, Ajzenberg D, Dardé ML, Collinet F, Tavernier P, Van Gucht S, Dorny P, Dierick K. Toxoplasma gondii and Neospora caninum in wildlife: common parasites in Belgian foxes and Cervidae?. Vet Parasitol 2011; 178: 64-69
• 29 Meerburg BG, De Craeye S, Dierick K, Kijlstra A. Neospora caninum and Toxoplasma gondii in brain tissue of feral rodents and insectivores caught on farms in the Netherlands. Vet Parasitol 2012; 184: 317-320