Bezerra Francisca Magnólia Diógenes Holanda, Vieira-Neto Antônio Eufrásio, Benevides Samara Casemiro, Tavares Kaio César Simiano, Ribeiro Antonia Deyse de Castro, Santos Sacha Aubrey Alves Rodrigues, Leite Gerlânia de Oliveira, Alves Magalhães Francisco Ernani, Campos Adriana Rolim
Universidade de Fortaleza, Núcleo de Biologia Experimental (NUBEX), Fortaleza, Ceará, Brazil.
Universidade Estadual do Ceará (UECE- CECITEC), Laboratório de Bioprospecção de Produtos Naturais e Biotecnologia (LBPNB), Tauá, Ceará, Brazil.
Planta Med. 2023 Apr;89(5):539-550. doi: 10.1055/a-1988-2098. Epub 2023 Jan 31.
This study evaluates the pharmacological potential of -jasmone (CJ) in adult zebrafish (; aZF). Initially, aZF (n = 6/group) were pretreated (20 µL; ) with CJ (0.1 or 0.3 or 1.0 mg/mL) or vehicle (0.5% Tween 80). The animals were submitted to acute toxicity and locomotion tests, pentylenetetrazole-induced seizure, carrageenan-induced abdominal edema, and cinnamaldehyde-, capsaicin-, menthol-, glutamate-, and acid saline-induced orofacial nociception. The possible mechanisms of anticonvulsant, anxiolytic, and antinociceptive action were evaluated. The involvement of central afferent fibers sensitive to cinnamaldehyde and capsaicin and the effect of CJ on the relative gene expression of TRPA1 and TRPV1 in the brain of aZF were also analyzed, in addition to the study of molecular docking between CJ and TRPA1, TRPV1 channels, and GABA receptors. CJ did not alter the locomotor behavior and showed pharmacological potential in all tested models with no toxicity. The anticonvulsant effect of CJ was prevented by flumazenil (GABAergic antagonist). The anxiolytic-like effect of CJ was prevented by flumazenil and serotonergic antagonists. The antinociceptive effect was prevented by TRPA1 and TRPV1 antagonists. Chemical ablation with capsaicin and cinnamaldehyde prevented the orofacial antinociceptive effect of CJ. Molecular docking studies indicate that CJ interacted with TRPA1, TRPV1, and GABA receptors. CJ inhibited the relative gene expression of TRPA1 and TRPV1. CJ has pharmacological potential for the treatment of seizures, anxiety, inflammation, and acute orofacial nociception. These effects are obtained by modulating the GABAergic and serotonergic systems, as well as the TRPs and ASIC channels.
本研究评估了茉莉酮(CJ)在成年斑马鱼(;aZF)中的药理潜力。最初,将aZF(每组n = 6)用CJ(0.1或0.3或1.0 mg/mL)或赋形剂(0.5%吐温80)预处理(20 µL;)。对动物进行急性毒性和运动测试、戊四氮诱导的癫痫发作、角叉菜胶诱导的腹部水肿以及肉桂醛、辣椒素、薄荷醇、谷氨酸和酸性生理盐水诱导的口面部伤害感受测试。评估了其抗惊厥、抗焦虑和抗伤害感受作用的可能机制。除了研究CJ与TRPA1、TRPV1通道和GABA受体之间的分子对接外,还分析了对肉桂醛和辣椒素敏感的中枢传入纤维的参与情况以及CJ对aZF大脑中TRPA1和TRPV1相对基因表达的影响。CJ未改变运动行为,且在所有测试模型中均显示出无毒性的药理潜力。氟马西尼(GABA能拮抗剂)可阻止CJ的抗惊厥作用。氟马西尼和5-羟色胺能拮抗剂可阻止CJ的抗焦虑样作用。TRPA1和TRPV1拮抗剂可阻止CJ的抗伤害感受作用。用辣椒素和肉桂醛进行化学消融可阻止CJ的口面部抗伤害感受作用。分子对接研究表明,CJ与TRPA1、TRPV1和GABA受体相互作用。CJ抑制TRPA1和TRPV1的相对基因表达。CJ具有治疗癫痫、焦虑、炎症和急性口面部伤害感受的药理潜力。这些作用是通过调节GABA能和5-羟色胺能系统以及瞬时受体电位通道(TRPs)和酸敏感离子通道(ASICs)获得的。