Acute Toxicity and Anti-Inflammatory Activity of ITrattinnickia rhoifolia/I Willd Using the IZebrafish/I Model

The species Trattinnickia rhoifolia Willd, (T. rhoifolia), which belongs to the Burseraceae family, is widely used in ethnopharmacological cultural practices by traditional Amazonian people for anti-inflammatory purposes, sometimes as their only therapeutic resource. Although it is used in teas, infusions, macerations and in food, the species is still unexplored in regard to its pharmacophoric potential and chemical profile. Therefore, the aim of this study was to conduct a phytochemical characterization of the hydroethanolic extract of T. rhoifolia leaves (HELTr) and to evaluate the acute toxicity and anti-inflammatory activity of this species using zebrafish (Danio rerio). The extract was analyzed by gas chromatography-mass spectrometry (GC-MS). The evaluation of the acute toxicity of the HELTr in adult zebrafish was determined using the limit test (2000 mg/kg), with behavioral and histopathological evaluations, in addition to the analysis of the anti-inflammatory potential of HELTr in carrageenan-induced abdominal edema, followed by the use of the computational method of molecular docking. The phytochemical profile of the species is chemically diverse, suggesting the presence of the fatty acids, ester, alcohol and benzoic acid classes, including propanoic acid, ethyl ester and hexadecanoic acid. In the studies of zebrafish performed according to the index of histopathological changes (IHC), the HELTr did not demonstrate toxicity in the behavioral and histopathological assessments, since the vital organs remained unchanged. Carrageenan-induced abdominal edema was significantly reduced at all HELTr doses (100, 200 and 500 mg/kg) in relation to the negative control, dimethyl sulfoxide (DMSO), while the 200 mg/kg dose showed significant anti-inflammatory activity in relation to the positive control (indomethacin). With these activities being confirmed by molecular docking studies, they showed a good profile for the inhibition of the enzyme Cyclooxygenase-2 (COX-2), as the interactions established at the sites of the receptors used in the docking study were similar to the controls (RCX, IMN and CEL). Therefore, the HELTr has an acceptable degree of safety for acute toxicity, defined in the analysis of behavioral changes, mortality and histopathology, with a significant anti-inflammatory action in zebrafish at all doses, which demonstrates the high pharmacophoric potential of the species. These results may direct future applications and drug development but s