Fatty amides (N-alkylamides) are bioactive lipids that are widely distributed in microorganisms, animals, and plants. The low yield in the extraction process of spilantol, a fatty amide, which is mainly related to its diverse biological effects, compromises its application on a large scale. Thus, this study proposes an alternative method to synthesise fatty amides from Bertholletia excelsa (AGBe) oil, with a chemical structure similar to that of spilantol. Carrageenan-induced abdominal oedema in vivo models 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 metabolising organs (liver, kidneys, and intestines). All doses of AGBe (100 mg/kg, 500 mg/kg, and 750 mg/kg) were effective in reducing oedema by 65%, 69%, and 95%, respectively, producing a dose–response effect compared to the control group, and spilantol-inhibited oedema by 48%. In the in silico study, with the use of molecular docking, it was observed that among the AGBe, the molecules 18:1, ω-7-ethanolamine, and 18:1, ω-9-ethanolamine stood out, with 21 interactions for COX-2 and 20 interactions for PLA₂, respectively, surpassing the spilantol standard with 15 interactions for COX-2 and PLA₂. The anti-inflammatory action hypothesis 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 was administered orally in zebrafish, it was not possible to determine the LD₅₀; it can be said that AGBe is effective and safe for anti-inflammatory activity.

Graphic abstract

中文翻译：

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Bertholletia excelsa 甘油三酯（巴西坚果）的脂肪乙醇酰胺：斑马鱼（Danio rerio）的抗炎作用和急性毒性评价

脂肪酰胺（N-烷基酰胺）是广泛分布于微生物、动物和植物中的生物活性脂质。千日菊醇是一种脂肪酰胺，其提取过程中的低收率主要与其多样化的生物学效应有关，影响了其大规模应用。因此，本研究提出了一种替代方法，用于从Bertholletia excelsa (AGBe) 油中合成脂肪酰胺，其化学结构与千日菊醇相似。角叉菜胶诱导的腹腔水肿体内模型用于斑马鱼（斑马鱼）。在体内研究中，口服 AGBe 没有产生毒性迹象。在组织病理学研究中，AGBe 并未引起主要代谢器官（肝、肾和肠）的显着变化。与对照组相比，所有剂量的 AGBe（100 mg/kg、500 mg/kg 和 750 mg/kg）分别有效地减少了 65%、69% 和 95% 的水肿，产生了剂量反应效应，和 spilantol 抑制性水肿 48%。在 in silico 研究中，利用分子对接，观察到在 AGBe 中，分子 18:1，ω-7-乙醇胺和 18:1，ω-9-乙醇胺脱颖而出，有 21 种相互作用PLA ₂的 COX-2 和 20 次相互作用分别超过了千日菊醇标准，COX-2 和 PLA _{2的 15 次相互作用}. 抗炎作用假说在计算机研究中得到证实，证明 AGBe 参与抑制酶 COX-2 和 PLA ₂的过程。因此，根据获得的所有结果以及在斑马鱼中口服 1000 mg/kg 剂量之前的事实，不可能确定 LD ₅₀；可以说，AGBe的抗炎活性是有效且安全的。

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