However, in contrast with other local effects that are produced by direct action of 4-(Aminomethyl)benzoic acid specific toxins, the edematogenic Sivelestat sodium tetrahydrate activity is, apparently, a result of a combined action of diverse toxins, rapidly inducing the release of endogenous inflammatory mediators. In fact, their modulation by endogenous mediators often reduces the effectiveness of antivenom, since it is capable of neutralizing the toxins, but cannot reduce inflammation caused by chemical mediators released by these toxins. Regarding our results with J. gossypiifolia extract, it was observed that the extract, by p.o. route, inhibited the edematogenic response by about 40% after 120 min of the venom injection. As can be observed in Figure 5A, the extract was active at 100 and 200 mg/kg, with the inhibitory effect starting from 90 min after venom injection. Regarding MPO activity, in the same way, the extract was active at 100 and 200 mg/kg, showing about 20% inhibition of the MPO activity. With i.p. treatment, even better results were obtained by the extract, as could be observed by the complete inhibition of the edematogenic activity after 120 min of venom injection. By i.p. route, the extract was able to reduce the MPO activity by about 50%. The different activity of the extract in both routes used is expected, since they have different biodisponibility profiles. This significant inhibition of MPO activity could indicate that the antiedematogenic effect presented by the extract could be related to an inhibition of cell migration, since this enzyme is a quantitative marker of inflammatory cell influx to paw tissue injected with venom. Regarding the possible mechanism by which the extract could be acting in this model, some hypothesis could be taken into account based on the experimental results obtained. Once the extract was inactive against Asp49 PLA2, a possible inhibition upon Lys49 PLA2 could be pointed out. Another possibility may be an inhibitory action upon SVMPs, since the extract also presented anti-hemorrhagic effect, as discussed previously. Additionally, another plausible hypothesis is that the extract could present potent anti-inflammatory activity and, so, may be able to reduce the inflammation produced by endogenous chemical mediators released by toxins.