Atividade neutralizante de jatropha gossypiifolia l. sobre enzimas do veneno de bothrops jararacussu

Abstract

The snake Bothrops jararacussu is the second leading cause of snakebite accidents in Brazil. Its venom is rich in metalloproteinases, phospholipases A₂, and L-amino acid oxidases-enzymes associated with severe local effects. Although antivenom therapy is the indicated treatment for the systemic neutralization of toxins, its efficacy against tissue damage is limited. In this context, the plant species Jatropha gossypiifolia L. emerges as a therapeutic alternative, given that its ethnopharmacobotanical use against envenomation is already documented. Thus, this study evaluated the antioxidant activity of extracts from the leaves, inflorescences, branches, and roots of J. gossypiifolia, as well as their inhibitory potential against the metalloproteinase and phospholipase A₂ activities present in B. jararacussu venom. The crude extract from the inflorescences exhibited the highest levels of enzyme inhibition (46.4 ± 1.3% and 72.4 ± 0.3% against metalloproteinases and phospholipases, respectively) and antioxidant activity (1,094 ± 20.4 µmol ET g⁻¹ and 1,567.9 ± 26.6 µmol ET g⁻¹ for the DPPH and FRAP assays, respectively); consequently, it was selected for fractionation. Among the fractions obtained (hexane, dichloromethane, ethyl acetate, and aqueous), the aqueous fraction demonstrated the greatest inhibitory activity (78.9 ± 1.1% for metalloproteinases and 79.6 ± 3.7% for phospholipases). Subsequently, the substances within this fraction were isolated using high-performance liquid chromatography. Mass spectrometry analysis led to the identification of the flavonoids orientin, isoorientin, vitexin, and isovitexin. All of them demonstrated an ability to inhibit the venom, notably orientin and isoorientin, which achieved inhibition results statistically equivalent to those of the anti-Bothrops antivenom; IC50 values were 168.0 ± 12.3 μM for isoorientin and 209.7 ± 9.0 μM for orientin in the proteolytic inhibition assay, and 112.6 ± 4.0 μM for isoorientin and 110.2 ± 2.6 μM for orientin in the phospholipase inhibition assay. The results demonstrate that J. gossypiifolia contains substances capable of interfering with key enzymatic activities of B. jararacussu venom, highlighting its potential as a source of bioactive compounds for antivenom applications.