Experimental Biology Centre, University of Fortaleza, Fortaleza, Brazil.
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza, Brazil.
Chem Biol Interact. 2019 Feb 1;299:37-43. doi: 10.1016/j.cbi.2018.11.018. Epub 2018 Nov 26.
This study aimed to evaluate the antinociceptive effect of oleanolic acid using adult zebrafish models of orofacial pain. Acute nociception was induced by formalin, capsaicin, cinnamaldehyde, menthol, acidified saline or glutamate (cutaneous modes) and hypertonic saline (corneal model). In another set of experiments, animals were pre-treated with naloxone, L-NAME, methylene blue, ketamine, camphor, HC-030031, mefenamic acid, ruthenium red or amiloride to investigate the mechanism of antinociception. The involvement of central afferent C-fibers was also investigated. A molecular docking was performed using the TRPV1 channel. Motor activity was evaluated with the open field test. Pre-treatment with oleanolic acid significantly reduced nociceptive behavior associated with acute pain. Antinociception was effectively inhibited by ruthenium red and capsaicin-induced desensitization. Presence of trpv1 was confirmed by RT-PCR in cerebral tissue of zebrafish. In line with in vivo experiments, docking studies indicated that oleanolic acid may interact with TRPV1. Results confirm the potential pharmacological relevance of oleanolic acid as an inhibitor of orofacial nociception mediated by TRPV1.
本研究旨在利用成年斑马鱼模型评估齐墩果酸的抗伤害感受作用。使用福尔马林、辣椒素、肉桂醛、薄荷醇、酸化盐水或谷氨酸（皮肤模式）和高渗盐水（角膜模型）诱导急性伤害感受。在另一组实验中，动物先用纳洛酮、L-NAME、亚甲蓝、氯胺酮、樟脑、HC-030031、甲芬那酸、钌红或阿米洛利预处理，以研究其抗伤害感受的机制。还研究了中枢传入 C 纤维的参与。使用 TRPV1 通道进行分子对接。使用旷场试验评估运动活性。齐墩果酸预处理显著减少了与急性疼痛相关的伤害感受行为。抗伤害感受作用被钌红和辣椒素诱导的脱敏有效抑制。RT-PCR 证实了斑马鱼脑组织中 trpv1 的存在。与体内实验一致，对接研究表明齐墩果酸可能与 TRPV1 相互作用。结果证实了齐墩果酸作为 TRPV1 介导的口腔伤害感受抑制剂的潜在药理学相关性。
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