INHIBITION OF THE MYOTOXIC AND HEMORRHAGIC ACTIVITIES OF CROTALID VENOMS BY ECLIPTA-PROSTRATA (ASTERACEAE) EXTRACTS AND CONSTITUENTS

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.