Pa. Melo et al., INHIBITION OF THE MYOTOXIC AND HEMORRHAGIC ACTIVITIES OF CROTALID VENOMS BY ECLIPTA-PROSTRATA (ASTERACEAE) EXTRACTS AND CONSTITUENTS, Toxicon, 32(5), 1994, pp. 595-603
The antimyotoxic and antihemorrhagic effects of Eclipta prostrata (EP)
and three of its constituents (wedelolactone, WE; stigmaterol, ST; an
d sitosterol, SI) were investigated. The myotoxicity of crotalid venom
s (Bothrops jararaca, Bothrops jararacussu and Lachesis muta), purifie
d myotoxins (both-ropstoxin, BthTX; bothropasin; and crotoxin), and po
lylysine was quantified in vitro by the release rate of creatine kinas
e (CK) from rat or mouse extensor digitorum muscles, and in vivo by th
e plasma CK activity in mice. The in vitro myotoxicity of the crotalid
venoms and myotoxins was neutralized by simultaneous exposure of the
muscles to an aqueous extract of EP or to WE. ST and SI were less effe
ctive than WE, but interacted synergistically with it. Both the EP ext
ract and WE failed to neutralize the in vitro myotoxic effects of poly
lysine. The in vivo myotoxicity of venoms and myotoxins was neutralize
d by their preincubation with the EP extract or WE. Intravenous admini
stration of the plant extract or WE attenuated the increase in plasma
CK activity induced by subsequent intramuscular injections of the crot
alid venoms or the myotoxins. EP and WE inhibited the hemorrhagic effe
ct of B. jararaca venom, as well as the phospholipase A, activity of c
rotoxin and the proteolytic activity of B. jararaca venom. The data pr
ovide direct evidence for antimyotoxic and antihemorrhagic effects of
EP and WE against the crotalid venoms responsible for most cases of en
venomation by snakebites in Brazil. These effects are interpreted as c
onsequences of antiproteolytic and antiphospholipase A(2) activities o
f EP and its constituents.