Universidade Estadual do Ceará, Centro de Ciências e Tecnologia, Programa de Pós-Graduação Ciências Naturais, Laboratório de Química de Produtos Naturais, Fortaleza, Ceará, Brazil.
Universidade de Fortaleza, Núcleo de Biologia Experimental (NUBEX), Fortaleza, Ceará, Brazil.
Biochem Biophys Res Commun. 2020 Dec 10;533(3):362-367. doi: 10.1016/j.bbrc.2020.07.107. Epub 2020 Sep 19.
Drugs used to treat pain are associated with adverse effects, increasing the search for new drugs as an alternative treatment for pain. Therefore, we evaluated the antinociceptive behavior and possible neuromodulation mechanisms of triterpene 3β, 6β, 16β-trihydroxylup-20(29)-ene (CLF-1) isolated from Combretum leprosum leaves in zebrafish. Zebrafish (n = 6/group) were pretreated with CLF-1 (0.1 or 0.3 or 1.0 mg/mL; i.p.) and underwent nociception behavior tests. The antinociceptive effect of CFL-1 was tested for modulation by opioid (naloxone), nitrergic (L-NAME), nitric oxide and guanylate cyclase synthesis inhibitor (methylene blue), NMDA (Ketamine), TRPV1 (ruthenium red), TRPA1 (camphor), or ASIC (amiloride) antagonists. The corneal antinociceptive effect of CFL-1 was tested for modulation by TRPV1 (capsazepine). The effect of CFL-1 on zebrafish locomotor behavior was evaluated with the open field test. The acute toxicity study was conducted. CLF-1 reduced nociceptive behavior and corneal in zebrafish without mortalities and without altering the animals' locomotion. Thus, CFL-1 presenting pharmacological potential for the treatment of acute pain and corneal pain, and this effect is modulated by the opioids, nitrergic system, NMDA receptors and TRP and ASIC channels.
用于治疗疼痛的药物与不良反应相关，这增加了对新药物的研究，以作为疼痛的替代治疗方法。因此，我们评估了从 Combretum leprosum 叶中分离得到的三萜 3β,6β,16β-三羟基齐墩果酸（CLF-1）在斑马鱼中的镇痛行为和可能的神经调制机制。将斑马鱼（每组 n = 6）用 CLF-1（0.1 或 0.3 或 1.0 mg/mL；腹腔注射）预处理，然后进行痛觉行为测试。测试了 CFL-1 对阿片类（纳洛酮）、硝化（L-NAME）、一氧化氮和鸟苷酸环化酶合成抑制剂（亚甲蓝）、NMDA（氯胺酮）、TRPV1（钌红）、TRPA1（樟脑）或 ASIC（阿米洛利）拮抗剂的镇痛作用的调制。用 TRPV1（辣椒素）测试了 CFL-1 对角膜镇痛作用的调制。用旷场试验评估了 CFL-1 对斑马鱼运动行为的影响。进行了急性毒性研究。CLF-1 可减少斑马鱼的疼痛行为和角膜疼痛，且无死亡率，也不改变动物的运动。因此，CFL-1 具有治疗急性疼痛和角膜疼痛的药理学潜力，这种作用由阿片类物质、硝化系统、NMDA 受体以及 TRP 和 ASIC 通道调制。
