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; and sitosterol, SI) were investigated. The myotoxicity of crotalid venoms (Bothrops jararaca, Bothrops jararacussu and Lachesis muta), purified myotoxins (bothropstoxin, BthTX; bothropasin; and crotoxin), and polylysine was quantified in vitro by the release rate of creatine kinase (CK) from rat or mouse extensor digitorum muscles, and in vivo by the 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 effective than WE, but interacted synergistically with it. Both the EP extract and WE failed to neutralize the in vitro myotoxic effects of polylysine. The in vivo myotoxicity of venoms and myotoxins was neutralized by their preincubation with the EP extract or WE. Intravenous administration of the plant extract or WE attenuated the increase in plasma CK activity induced by subsequent intramuscular injections of the crotalid venoms or the myotoxins. EP and WE inhibited the hemorrhagic effect of B. jararaca venom, as well as the phospholipase A2 activity of crotoxin and the proteolytic activity of B. jararaca venom. The data provide direct evidence for antimyotoxic and antihemorrhagic effects of EP and WE against the crotalid venoms responsible for most cases of envenomation by snakebites in Brazil. These effects are interpreted as consequences of antiproteolytic and antiphospholipase A2 activities of EP and its constituents.