Aspidosperma Species as Sources of Antimalarials. Part III. A Review of Traditional Use and Antimalarial Activity^[*]

Abstract

Several plant species belonging to the genus Aspidosperma are traditionally used in Brazil and other Meso- and South American countries for the treatment of malaria and fevers. These traditional uses were motivation for this review. A literature survey completed for this review has identified scientific bibliographical references to the use of 24 Aspidosperma species to treat malaria/fevers and to 19 species that have had their extracts and/or alkaloids evaluated, with good results, for in vitro and/or in vivo antimalarial activity. Indole alkaloids are typical constituents of Aspidosperma species. However, only 20 out of more than 200 known indole alkaloids isolated from this genus have been assayed for antimalarial activity. These data support the potential of Aspidosperma species as sources of antimalarials and the importance of research aimed at validating their use in the treatment of human malaria.

Key words

Aspidosperma spp. - Apocynaceae - malaria - Plasmodium falciparum - antimalarial activity

^* For Part I see [48], for Part II see [36]. Part of RCP Doctorate Thesis at PPGCF, UFMG, Belo Horizonte, MG, Brazil.

^** All authors contributed equally to this article.

• References

• 1 World Health Organization. World Malaria Report 2009. Available at http://whqlibdoc.who.int/publications/2009/9789241563901_eng.pdf Accessed November 25, 2009.
• 2 World Health Organization. World Malaria Report 2008. Available at http://whqlibdoc.who.int/publications/2008/9789241563697_eng.pdf Accessed November 22, 2009.
• 3 Oliveira-Ferreira J, Lacerda MVG, Brasil P, Ladislau JLB, Tauil PL, Daniel-Ribeiro CT. Malaria in Brazil: an overview. Malar J 2010; 9: 115-130
• 4 World Health Organization. World Malaria Report 2011. Available at http://www.who.int/malaria/world_malaria_report_2011/9789241564403_eng.pdf Accessed January 13, 2011.
• 5 Oliveira AB, Dolabela MF, Braga FC, Jacome RL, Varotti FP, Povoa MM. Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids. An Acad Bras Cienc 2009; 81: 715-740
• 6 Castellanos JRG, Prieto JM, Heinrich M. Red Lapacho (Tabebuia impetiginosa)–a global ethnopharmacological commodity?. J Ethnopharmacol 2009; 121: 1-13
• 7 Newman DJ, Cragg GM. Natural products as sources of new drugs over the last 25 years. J Nat Prod 2007; 70: 461-477
• 8 Ginsburg H, Deharo E. A call for using natural compounds in the development of new antimalarial treatments – an introduction. Malar J 2011; 10 (Suppl. 01) S1
• 9 Batista R, Junior AJS, Oliveira AB. Plant-derived antimalarial agents: new leads and efficient phytomedicines. Part II. Non-alkaloidal natural products. Molecules 2009; 14: 3037-3072
• 10 Verpoorte R, Choi Y, Mustafa N, Kim H. Metabolomics: back to basics. Phytochem Rev 2008; 7: 525-537
• 11 Wagner H. Natural products chemistry and phytomedicine research in the new millennium: new developments and challenges. Arkivoc 2004; VII: 277-284
• 12 Ulrich-Merzenich G, Zeitler H, Jobst D, Panek D, Vetter H, Wagner H. Application of the “-Omic-” technologies in phytomedicine. Phytomedicine 2007; 14: 70-82
• 13 Verpoorte R, Choi YH, Kim HK. Ethnopharmacology and systems biology: a perfect holistic match. J Ethnopharmacol 2005; 100: 53-56
• 14 Deharo E, Ginsburg H. Analysis of additivity and synergism in the antiplasmodial effect of purified compounds from plant extracts. Malar J 2011; 10 (Suppl. 01) S5
• 15 Lorenzi H. Árvores Brasileiras: manual de identificação e cultivo de plantas arbóreas nativas do Brasil. 2nd. edition. São Paulo: Plantarum; 1998: 365
• 16 Perez-Arbeláez E. Plantas útiles de Colombia. 5th edition. Bogotá: Fondo Fen Colombia; 1996: 831
• 17 Pio-Corrêa M. Dicionário de plantas úteis do Brasil e das exóticas cultivadas. Rio de Janeiro: Ministério da Agricultura; 1978: 687
• 18 Rizzini CT. Árvores e madeiras úteis do Brasil: manual de dendrologia brasileira. 2nd. edition. São Paulo: E. Blücher; 2000: 312
• 19 Schultes RE, Raffauf RF. The healing forest: medicinal and toxic plants of the northwest Amazonia. 1st. edtion. Portland: Dioscorides Press; 2003: 500
• 20 Koch I, Rapini A, Kinoshita LS, Simões AO, Spina AP. Apocynaceae. Lista de Espécies da Flora do Brasil. Jardim Botânico do Rio de Janeiro. Available at http://reflora.jbrj.gov.br/jabot/floradobrasil/FB21892 Accessed December 8, 2013.
• 21 Sennblad B, Bremer B. Classification of Apocynaceae s.l. according to a new approach combining Linnaean and phylogenetic taxonomy. Syst Biol 2002; 51: 389-409
• 22 Woodson RE. Studies in the Apocynaceae. VIII. An Interim Revision of the Genus Aspidosperma Mart. & Zucc. Ann Mo Bot Gard 1951; 38: 119-206
• 23 Marcondes-Ferreira W, Kinoshita L. Uma nova divisão infragenerica para Aspidosperma Mart. (Apocynaceae).[A new infrageneric division on Aspidosperma Mart. (Apocynaceae)]. Rev Brasil Bot 1996; 19: 203-214
• 24 Lista de Espécies da Flora do Brasil. Available at http://floradobrasil.jbrj.gov.br/jabot/listaBrasil/PrincipalUC/PrincipalUC.do Accessed November 29, 2011.
• 25 Tropicos. Missouri Botanical Garden – Tropicos Specimen Data Base. Available at http://www.tropicos.org/NameSearch.aspx?name=Aspidosperma&common%20name= Accessed November 30, 2011.
• 26 The Plant List. (2010). Version 1. Available at http://www.theplantlist.org/tpl/search?q=Aspidosperma Accessed November 29, 2011.
• 27 Dolabela MF. Atividade antiplasmódica e citotoxicidade de Esenbeckia febrifuga (A.St-Hil.) Juss. ex Mart. (Rutaceae) e de espécies do gênero Aspidosperma (Apocynaceae) [dissertation]. Belo Horizonte: Universidade Federal de Minas Gerais; 2007
• 28 Mesquita M, Grellier P, Mambu L, De Paula J, Espindola L. In vitro antiplasmodial activity of Brazilian Cerrado plants used as traditional remedies. J Ethnopharmacol 2007; 110: 165-170
• 29 Pereira MM, Jácome R, Alcântara A, Alves RB, Raslan DS. Alcalóides indólicos isolados de espécies do gênero Aspidosperma (Apocynaceae). Quim Nova 2007; 30: 970-983
• 30 Oliveira V, Freitas M, Mathias L, Braz-Filho R, Vieira I. Atividade biológica e alcalóides indólicos do gênero Aspidosperma (Apocynaceae): uma revisão. Rev Bras Pl Med 2009; 11: 92-99
• 31 Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976; 193: 673-675
• 32 Becker ER. Report on 35 drugs and three plant materials tested against Plasmodium lophurae in the white Pekin duck. Iowa State Coll J Sci 1949; 23: 189-194
• 33 Wasicky R, Unti O, Barbieri E. Quinine and alkaloids in Brazil. An Fac Farm Odontol Univ São Paulo 1942; 3: 137
• 34 Dominguez J. Malaria treatment with Aspidosperma quebracho blanco . Rev Farm (Buenos Aires) 1932; 73: 82
• 35 Loizaga N, Sagastume L. Malaria treatment with Quechuol-Dominguez. Sem Med Buenos Aires 1935; 2: 562-566
• 36 Weniger B, Robledo S, Arango GJ, Deharo E, Aragon R, Munoz V, Callapa J, Lobstein A, Anton R. Antiprotozoal activities of Colombian plants. J Ethnopharmacol 2001; 78: 193-200
• 37 Cabral JA, McChesney JD, Milhous WK. A new antimalarial quassinoid from Simaba guianensis . J Nat Prod 1993; 56: 1954-1961
• 38 Bourdy G, Oporto P, Gimenez A, Deharo E. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part VI. Evaluation of the antimalarial activity of plants used by Isoceno-Guarani Indians. J Ethnopharmacol 2004; 93: 269-277
• 39 Kvist LP, Christensen SB, Rasmussen HB, Mejia K, Gonzalez A. Identification and evaluation of Peruvian plants used to treat malaria and leishmaniasis. J Ethnopharmacol 2006; 106: 390-402
• 40 Brandão MG, Grandi TS, Rocha EM, Sawyer DR, Krettli AU. Survey of medicinal plants used as antimalarials in the Amazon. J Ethnopharmacol 1992; 36: 175-182
• 41 Mitaine-Offer AC, Sauvain M, Valentin A, Callapa J, Mallie M, Zeches-Hanrot M. Antiplasmodial activity of Aspidosperma indole alkaloids. Phytomedicine 2002; 9: 142-145
• 42 Mitaine AC, Mesbah K, Richard B, Petermann C, Arrazola S, Moretti C, Zeches-Hanrot M, Men-Olivier LL. Alkaloids from Aspidosperma species from Bolivia. Planta Med 1996; 62: 458-461
• 43 Dolabela MF, Oliveira SG, Peres JM, Nascimento JM, Póvoa MM, Oliveira AB. In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil). An Acad Bras Cienc 2012; 84: 899-910
• 44 Carvalho LH, Brandão MG, Santos-Filho D, Lopes JL, Krettli AU. Antimalarial activity of crude extracts from Brazilian plants studied in vivo in Plasmodium berghei-infected mice and in vitro against Plasmodium falciparum in culture. Braz J Med Biol Res 1991; 24: 1113-1123
• 45 Andrade-Neto VF, Pohlit AM, Pinto AC, Silva EC, Nogueira KL, Melo MR, Henrique MC, Amorim RC, Silva LF, Costa MR, Nunomura RC, Nunomura SM, Alecrim WD, Alecrim MG, Chaves FC, Vieira PP. In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants. Mem Inst Oswaldo Cruz 2007; 102: 359-365
• 46 Oliveira AB, Dolabela MF, Póvoa MM, Santos CAM, Varotti FP. Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole. Mal J 2010; 9 (Suppl. 02) O9
• 47 Torres ZES, Silveira ER, Rocha e Silva LF, Lima ES, Vasconcellos MC, Andrade Uchoa DE, Filho RB, Pohlit AM. Chemical composition of Aspidosperma ulei Markgr. and antiplasmodial activity of selected indole alkaloids. Molecules 2013; 18: 6281-6297
• 48 Rocha e Silva LF, Montoia A, Amorim RC, Melo MR, Henrique MC, Nunomura SM, Costa MR, Andrade Neto VF, Costa DS, Dantas G, Lavrado J, Moreira R, Paulo A, Pinto AC, Tadei WP, Zacardi RS, Eberlin MN, Pohlit AMLF. Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog. Phytomedicine 2012; 20: 71-76
• 49 Cirino JJV, Belletato P, Dantas SO, Ribeiro L, Ferreira GR, Santos HF. Estrutura e propriedades de elipticinas. Quim Nova 2005; 28: 30-36
• 50 Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J Ethnopharmacol 2005; 100: 72-79
• 51 Mans DR, da Rocha AB, Schwartsmann G. Anti-cancer drug discovery and development in Brazil: targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds. Oncologist 2000; 5: 185-198
• 52 Passemar C, Salery M, Soh PN, Linas MD, Ahond A, Poupat C, Benoit-Vical F. Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules. Phytomedicine 2011; 18: 1118-1125
• 53 Mitaine AC, Weniger B, Sauvain M, Lucumi E, Aragon R, Zeches-Hanrot M. Indole alkaloids from the trunk bark of Aspidosperma megalocarpon. Planta Med 1998; 64: 487
• 54 Büchi G, Warnhoff E. The structure of uleine. J Am Chem Soc 1959; 81: 4433-4434
• 55 Joule J. The uleine-ellipticine-vallesamine group. In: Saxton JE, editor The chemistry of heterocyclic compounds, indoles: the monoterpenoid indole alkaloids. 1st edition. Cleveland: John Wiley & Sons; 2009: 886
• 56 Nardin JM, de Souza WM, Lopes JF, Florao A, de Moraes Santos CA, Weffort-Santos AM. Effects of Himatanthus lancifolius on human leukocyte chemotaxis and their adhesion to integrins. Planta Med 2008; 74: 1253-1258
• 57 Jácome R, Oliveira A, Raslan DS, Wagner H. Estudo químico e perfil cromatográfico das cascas de Aspidosperma parvifolium A. DC. (“pau-pereira”). Quim Nova 2004; 27: 897-900
• 58 PubChem Substance. Uleine-Substance Summary. Available at http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=115962 Accessed August 11, 2013.
• 59 Willcox ML, Bodeker G. Traditional herbal medicines for malaria. BMJ 2004; 329: 1156-1159
• 60 Wright CW. Recent developments in research on terrestrial plants used for the treatment of malaria. Nat Prod Rep 2010; 27: 961-968
• 61 Oliveira AB, Dolabela MF, Rocha FD, Gomes FMA, Neiva RMT, Jácome RLRP. Extrato e fração padronizados de cascas de Aspidosperma parvifolium e/ou uleina e sua composição farmacêutica. Filing date: Dec 23, 2009. PI0905584 – 3. Assignee: Universidade Federal de Minas Gerais – UFMG. Belo Horizonte, MG, Brazil.
• 62 Araújo jr. JX, Antheaume C, Trindade RCP, Schmitt M, Bourguignon JJ, SantʼAna AEG. Isolation and characterisation of the monoterpenoid indole alkaloids of Aspidosperma pyrifolium . Phytochem Rev 2007; 6: 183-188
• 63 Grenand P, Moretti C, Jacquemin H, Prévost M. Pharmacopées traditionnelles en Guyane Créoles, Polikur, Wayapi. 1st. edition. Montpellier: IRD Édtions; 2006: 816
• 64 Barbosa WLR, Tavares ICC, Soares DC. Alcaloides de Aspidosperma auriculatum Standl. Braz J Pharmacogn 2003; 13: 6-8
• 65 Pittier H. Manual de las plantas usuales de Venezuela y su suplemento. 2nd. edition. Caracas: Fundación Eugenio Mendoza; 1978: 620
• 66 Quignard ELJ, Martin Pohlit A, Nunomura SM, Da Silva Pinto AC, Mustafa dos Santos EV, Reis de Morais SK, Alecrim AM, Da Silva Pedroso AC, Brito Cyrino BR, Melo CS. Screening of plants found in Amazonas state for lethality towards brine shrimp Artemia franciscana . Acta Amazonica 2003; 33: 93-104
• 67 Brandão MGL, Botelho MGA, Krettli AU. Quimioterapia experimental antimalárica com produtos naturais: I. Uma abordagem mais racional?/Experimental antimalarial chemotherapy with natural products: I. A more rational approach?. Cienc Cult 1985; 37: 1152-1163
• 68 Milliken W. Traditional anti-malarial medicine in Roraima, Brazil. Econ Bot 1997; 51: 212-237
• 69 Mejía CK, Rengifo SE. Plantas medicinales de uso popular en la Amazonía Peruana. 1st. edition. Lima: Tarea Asociación Gráfica Educativa; 1995: 286
• 70 Pérez D. Etnobotánica medicinal y biocidas para malaria en la región Ucayali. Folia Amazónica 2002; 13: 2
• 71 Duke JA, Vasquez R. Amazonian ethnobotanical dictionary. 1st. edition. Florida: CRC Press; 1994: 224
• 72 Milliken W, Albert B. The use of medicinal plants by the Yanomami Indians of Brazil. Econ Bot 1996; 50: 10-25
• 73 DeFilipps RA, Maina SL, Crepin J. Medicinal Plants of the Guianas (Guyana, Surinam, French Guiana). Part 1 Acanthaceae – Combretaceae. Avaliable at. http://botany.si.edu/bdg/medicinal/Medicinal_plants_master.pdf Accessed July 28, 2011.
• 74 Almeida MR, Lima JA, dos Santos NP, Pinto AC. Pereirina: o primeiro alcalóide isolado no Brasil?. Braz J Pharmacogn 2009; 19: 942-952
• 75 Botsaris AS. Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal. J Ethnobiol Ethnomed 2007; 3: 18-19
• 76 Milliken W, Albert B. The use of medicinal plants by the Yanomami Indians of Brazil, Part II. Econ Bot 1997; 51: 264-278
• 77 Del Vitto LA, Petenatti E, Petenatti M. Recursos herbolarios de San Luis (República Argentina). Primera parte: Plantas nativas. Multequina 1997; 6: 49-66
• 78 Freitas ADD. Aspectos tecnológicos e morfoanatômicos de sementes maduras, plântulas e plantas jovens de Aspidosperma spruceanum Benth. Ex Mull. Arg. (Apocynaceae) [dissertation]. Belém: Universidade Federal Rural da Amazônia e Museu Paraense Emílio Goeldi; 2008
• 79 Di Stasi LC. Plantas medicinais na Amazônia e na Mata Atlântica. 2nd. edition. São Paulo: UNESP; 2002: 592
• 80 Mariath IR, Falcão HS, Barbosa-Filho JM, Sousa LCF, Tomaz ACA, Batista LM, Diniz MFFM, Athayde-Filho PF, Tavares JF, Silva MS. Plants of the American continent with antimalarial activity. Braz J Pharmacogn 2009; 19: 158-191
• 81 Muñoz V, Sauvain M, Bourdy G, Callapa J, Bergeron S, Rojas I, Bravo JA, Balderrama L, Ortiz B, Gimenez A, Deharo E. A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part I. Evaluation of the antimalarial activity of plants used by the Chacobo Indians. J Ethnopharmacol 2000; 69: 127-137
• 82 Krettli LG, de Paula RC, Varotti FP, Pereira MM, Oliveira AJB, Krettli AU. Antimalarial activity of extracts from Aspidosperma plants tested in vitro against Plasmodium falciparum drug resistant parasites and in animal models. XXIV Meeting of the SBPz. Águas de Lindóia, São Paulo: Brazilian Society of Protozoology; 2008