Bothrops neuwiedi

Januario AH, Santos SL, Marcussi S, Mazzi MV, Pietro RC, Sato DN, Ellena J, Sampaio SV, Franca SC, Soares AM.

Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties.

Many plants are used in traditional medicine as active agents against various effects induced by snakebite. Few attempts have been made however to identify the nature of plant natural products with anti-ophidian properties. Baccharis trimera (Less) DC (Asteraceae), known in Brazil as carqueja, has been popularly used to treat liver diseases, rheumatism, diabetes, as well as digestive, hepatic and renal disorders. The active component was identified as 7alpha-hydroxy-3,13-clerodadiene-16,15:18,19-diolide, C₂₀H₂₈O₅, (clerodane diterpenoid, Bt-CD). We report now the anti-proteolytic and anti-hemorrhagic properties against snake venoms of a Bt-CD inhibitor from B. trimera. Bt-CD exhibited full inhibition of hemorrhage and proteolytic activity caused by Bothrops snake venoms. The inhibitor was able to neutralize the hemorrhagic, fibrinogenolytic and caseinolytic activities of class P-I and III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. No inhibition of the coagulant activity was observed. Bt-CD also partially inhibited the edema induced by other crude venoms, metalloproteases, basic and acidic phospholipases A₂. To further elucidate the inhibitory specificity of Bt-CD against metalloproteases isolated from snake venoms, a deeper understanding of its structure and function is necessary. Furthermore, the potential use of these inhibitors to complement anti-venom as an alternative treatment of snakebite envenomations needs to be evaluated in future studies.

Fernandes, VC(1); Marcussi, S(2); Amui, SF(3); França, SC(1); Pereira, AMS(1); Soares, AM(3)

Efeito inibitório do extrato aquoso de folhas de Scleria pterota sobre diferentes atividades tóxicas e farmacológicas de venenos de serpentes

Estudos de mecanismos de ação de proteínas de venenos estão sendo desenvolvidos, através de ensaios com diferentes extratos de plantas e inibidores naturais isolados destas. O extrato e os venenos/ou toxinas foram incubados por 30 min a 37°C em diferentes proporções e posteriormente submetidos aos diferentes ensaios enzimáticos e biológicos. O extrato mostrou-se eficiente em inibir a atividade fosfolipásica dos venenos de Bothrops jararacussu e B. alternatus, não tendo efeito sobre os venenos de B. moojeni, B. neuwiedi e Crotalus durissus terríficus, nas proporções de 1:100 e 1:200. A coagulação induzida pelos venenos foi totalmente inibida na presença do extrato em proporção de 1:10. A hemorragia induzida por B. jararacussu, B. moojeni, B. alternatus e B. neuwiedi foi inibida pelo extrato na proporção de 1:50, mostrando maior inibição para os dois primeiros venenos. A eletroforese demonstrou que o extrato não degrada as proteínas dos venenos de serpentes, sugerindo a possibilidade de interações específicas entre os inibidores vegetais e as toxinas alvo. Assim, extrato de S. pterota inibiu as atividades enzimáticas e tóxicas dos venenos de serpentes interagindo de forma diferente para cada um deles, sem alterar a integridade das proteínas que os compõe. Os aspectos abordados neste trabalho poderão trazer informações complementares sobre mecanismos de ação destes venenos.

CONIC 2003

^aMaiorano VA , ^b,cMarcussi S, ^aDaher MA, ^a,cOliveira CZ, ^dCouto LB, ^dGomes OA, ^aFranca SC, ^cSoares AM, ^aPereira PS.

Antiophidian properties of the aqueous extract of Mikania glomerata

Aqueous extracts, prepared from dried or fresh roots, stems or leaves of Mikania glomerata, a plant found in Mata Atlantica in Southeastern Brazil, were able to efficiently neutralize different toxic, pharmacological, and enzymatic effects induced by venoms from Bothrops and Crotalus snakes. Phospholipase A₂ activity and the edema induced by Crotalus durissus terrificus venom were inhibited around 100 and approximately 40%, respectively, although this inhibition was only partial for Bothrops venoms. The hemorrhagic activity of Bothrops venoms (Bothrops altenatus, Bothrops moojeni, Bothrops neuwiedi, and Bothrops jararacussu) was significantly inhibited by this vegetal species, while the clotting activity of Crotalus durissus terrificus, Bothrops jararacussu, and Bothrops neuwiedi venoms was totally inhibited. Although, the mechanism of action of Mikania glomerata extract is still unknown, the finding that no visible change was detected in the electrophoretic pattern of snake venom after incubation with the extract excludes proteolytic degradation as a potential mechanism. Since the extract of Mikania glomerata significantly inhibited the studied snake venoms, it may be used as an alternative treatment to serumtherapy and, in addition, as a rich source of potential inhibitors of PLA₂s, metalloproteases and serineproteases, enzymes involved in several physiopathological human and animal diseases.

XII Congresso de Iniciação Científica da Universidade Federal de São Carlos - UFSCar