Eclipta prostrata extract and wedelolactone antagonize Apis mellifera venom activities

Africanized bees are a hybrid species that respond to threatening stimuli, leading to mass attack accidents. Bee envenoming can trigger various clinical conditions due to the complex composition of bee venom. The Eclipta prostrata (EP) plant, commonly used in folk medicine, contains several bioactive compounds, including wedelolactone (WEL), which has biological properties. This study aims to evaluate the effects of EP extract and WEL on different bee venom activities. Bee venom enzymatic and hemolytic activities were inhibited by EP extract and partially reduced by WEL at concentrations ranging from 0.3 to 150 μM, depending on the experiment. Anti-myotoxic in vitro effects were evaluated in isolated the extensor digitorum longus muscle of mice. Both antagonists (EP 1, 3 and 10 μg/mL and WEL 1, 3, and 10 μM) showed concentration-dependent anti-myotoxic effects in vitro, reducing venom-induced CK release rate from 13.29 ± 0.85 to 3.11 ± 0.64 U/g/h (EP 10 μg/mL) and from 11.77 ± 1.42 to 1.18 ± 0.34 U/g/h (WEL 10 μM), after 90 min of perfusion. In the in vivo assays, EP extract (50 mg/kg) reduced the effects of bee venom (1 mg/kg) only in the preincubation protocol, attenuating myotoxicity and local inflammatory responses, as assessed by plasma CK and myeloperoxidase activities, respectively. Furthermore, WEL showed an antagonistic effect only on the local inflammatory response in the pretreatment protocol, reducing the venom effect by approximately 40%. In this condition, WEL (30 mg/kg) was administered 30 min prior to venom (1 mg/kg) injection. There was no change in hemoconcentration or lethality induced by bee venom in either preincubation (EP 50 mg/kg; WEL 30 mg/kg) or pretreatment (EP 250 + 250 mg/kg; WEL 30 mg/kg) protocols. Finally, the EP extract and its isolated substance, WEL, reduced toxic activities in vitro. Further in vivo studies are required to understand the effects of the antagonists.