Topic utilization of sesquiterpene lactone fromMilleria quinqueflora on treatment of bothropic envenomation in rabbits 

  A prominent feature of envenomation caused by snakes of the Bothrops genus is the intense local effect, including pain, edema, hemorrhage and tissue necrosis (Barraviera and Pereira, 1994). The pathogenesis of these effects has been related to the effects of proteases, phospholipases, and hemorrhagic factors (Kamiguti et al., 1996). 

  The only acceptable treatment to Bothrops genus envenomation is the administration of specific anti-venom. If anti-venom administration is rapidly initiated after envenomation, neutralization of systemic effects is usually achieved. However, neutralization of local tissue damage is a more difficult task. In a number of snake bite cases, lack of neutralization of local effects results in permanent sequelae with tissue loss (Wen, 2000). 

Recently, it was demonstrated that topic application of an extract from Asteraceae Milleria quinqueflora has positive effects in the treatment of local snake bite envenomation. The mainly effective secondary metabolites of this plant are sesquiterpene lactones (SL) from the germacranolide type. It was shown that they inhibit the transcription factor NF-kB (Castro et al., 2000), a central mediator of the immune system which regulates the transcription of genes encoding various inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes, like iNOS or COX-2 (Baeuerle and Henkel, 1994; Barnes and Karin, 1997). In general, SLs are known for their various biological, pharmacological, and especially their anti-inflammatory activities (Schmidt, 1999). Besides their NF-kB inhibitory activity they modulate many processes that influence inflammatory reactions, for example: oxidative phosphorylation, platelet aggregation, histamine and serotonin release (Hall et al., 1980).

In a previous study (Castro et al., 2000), it was investigated 4b,15-epoxy-miller-9-Z-enolide, a sesquiterpene lactone isolated from Milleria quinqueflora for its properties against the local effects of Bothrops alternatus venom in rabbits.