Fatty Ethanolamide of Bertholletia Excelsa Triglycerides (Brazil nuts): Anti-Inflammatory Action and Acute Toxicity Evaluation in Zebrafish (Danio rerio)

Abstract

Fatty amides (N-alkylamides) are a group of bioactive lipids widely distributed in microorganisms, animals, and plants. The low yield in the extraction process of spilantol, a grease amide, which has been related mainly to diverse biological effects, compromises its application on a large scale. Thus, this study proposed an alternative to the synthesis of fatty amides from Bertholletia excelsa (AGBe) oil, with a chemical structure similar to that of spilantol. In vivo models induced by carrageenan were used in Zebrafish (Danio rerio). In in vivo studies, oral AGBe produced no signs of toxicity. In the histopathological study, AGBe did not cause significant changes in the main metabolizing organs (liver, kidneys, and intestines). In the anti-inflammatory evaluation, all doses (45 mg/kg, 500 mg/kg, and 1000 mg/kg) were effective, significantly reducing edema and producing a dose-response effect when compared to spilantol. In the in silico study, with the use of molecular docking, he showed that among the AGBe, the molecules 18:1, ω-7-ethanolamine and 18:1, ω-9-ethanolamine stood out, which had 21 interactions for COX-2 and 20 interactions for PLA2, respectively, surpassing the spilantol standard with 15 interactions for COX-2 and PLA2. The hypothesis of anti-inflammatory action was confirmed in the in silico study, demonstrating the involvement of AGBe in the process of inhibiting the enzymes COX-2 and PLA2. Therefore, based on all the results obtained and the fact that until the dose of 1000 mg/kg, orally, in zebrafish, it was not possible to determine the LD50, it can be said that AGBe is effective and safe for the activity anti-inflammatory.