969 Braz J Med Biol Res 37(7) 2004 Neutralization of Bothrops asper venom effects by plant extracts Brazilian Journal of Medical and Biological Research (2004) 37: 969-977 ISSN 0100-879X Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia 1 Grupo de Ofidismo y Escorpionismo, Facultad de Medicina, 2 Herbario, and 3 Facultad de Química Farmacéutica, Universidad de Antioquia, Medellín, Colombia V. Núñez 1 , R. Otero 1 , J. Barona 1 , M. Saldarriaga 1 , R.G. Osorio 1 , R. Fonnegra 1,2 , S.L. Jiménez 1,3 , A. Díaz 1 and J.C. Quintana 1 Abstract We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae), Struthanthus orbicularis (Lorantha- ceae) and Gonzalagunia panamensis (Rubiaceae); the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bigno- niaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of varying amounts of each extract with either 1.0 μg venom for the edema-forming effect or 2.0 μg venom for the defibrinating effect, the mixture was injected subcuta- neously (sc) into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200 μg/mouse) partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition), with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 μg/mouse) also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection), the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon. Correspondence R. Otero Centro de Investigaciones Médicas Facultad de Medicina Universidad de Antioquia A.A. 1226, Medellín Colombia Fax: +57-4-263-1914 E-mail: rafaotero@epm.net.co Research supported by the Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología Francisco José de Caldas (Colciencias) and by Universidad de Antioquia. Received June 2, 2003 Accepted February 26, 2004 Key words • Neutralization • Edema • Defibrination • Coagulation • Bothrops asper venom • Plant extracts