Programa de PósGraduação em Ciências Naturais, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
Rede Nordeste de Biotecnologia, Universidade Estadual do Ceará, Fortaleza, Ceará, Brazil.
Chem Biodivers. 2024 Aug;21(8):e202400786. doi: 10.1002/cbdv.202400786. Epub 2024 Jul 3.
This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors.
本研究旨在探讨从 E. bezerrae 中分离出的托烷生物碱 (EB7) 的抗炎和镇痛作用。评估了 EB7 的镇痛作用是否与离子通道有关，以及其在成年斑马鱼 (Zfa) 中的抗炎作用。还进行了 EB7 与 COX-1 和 2 的对接研究。在 96 小时的分析中，测试剂量的 EB7（4、20 和 40mg/kg）对 Zfa 没有任何毒性作用（LD50>40mg/kg）。它们没有对动物的运动行为产生任何改变。此外，EB7 表现出有希望的药理作用，因为它可以预防高渗盐水、辣椒素、甲醛和酸盐水引起的疼痛行为。EB7 的镇痛作用被阿米洛利阻断，这涉及到 ASICs 在 Zfa 中的神经调节。在评估抗炎活性时，观察到 40mg/kg 的 EB7 剂量可减少 κ-卡拉胶 3.5%引起的水肿，这表明其作用类似于布洛芬。分子对接结果表明，与布洛芬对照相比，EB7 对两个评估靶点表现出更好的亲和力能量，这些靶点在共晶化的 COX-1 和 2 抑制剂的不同部位结合。
