评估薄荷黄酮在酒精戒断的成年斑马鱼中的抗焦虑潜力:体内和体外研究

Receptors Pub Date : 2024-05-10 DOI:10.3390/receptors3020011
L. S. Frota, W. M. B. da Silva, Daniela Ribeiro Alves, Sacha Aubrey Alves Santos Rodrigues, Gabriela Alves do Nascimento, F. E. A. Magalhães, A. R. Campos, S. D. de Morais
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摘要

长期饮用酒精饮料会导致血清素水平失调,影响神经递质并引发焦虑症状。在这种情况下,本研究的目的是评估天然化合物金黄酮的抗焦虑潜力和可能的作用机制,以对抗酒精戒断对成年斑马鱼(aZF)行为造成的有害影响。实验结果表明,在长达96小时的分析过程中,门冬酰胺黄酮不会改变斑马鱼的运动,也不会对其产生毒性,中位致死浓度(LC50)大于1.0毫克/毫升。格拉司琼能逆转焦虑,这表明门冬酰胺黄酮的抗焦虑作用依赖于5-羟色胺能5-HT3A/3B受体。此外,门冬酰胺黄酮还能逆转氟马西尼预处理引起的焦虑,这表明它依赖于 GABAA 受体。所测试的三种浓度的门黄酮都能有效治疗酒精戒断引起的焦虑。硅学分析验证了体内结果,支持了这样一种观点,即与参考化合物相比,门冬酰胺黄酮以更稳定的方式与蛋白质发生相互作用。人们对治疗焦虑症的天然替代品越来越感兴趣,而门冬酰胺黄酮是一种新型抗焦虑化合物的潜在候选者,它能专门作用于 5HT3A/3B 和 GABA 能血清素能通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An Evaluation of the Anxiolytic Potential of Amentoflavone in Adult Zebrafish Undergoing Alcohol Withdrawal: In Vivo and In Silico Studies
The constant use of alcoholic beverages can deregulate serotonin levels, affecting neurotransmitters and triggering symptoms of anxiety. In this context, the objective of this work was to evaluate the anxiolytic potential and possible action mechanisms of the natural compound amentoflavone against the deleterious effects caused by alcohol withdrawal on the behavior of adult zebrafish (aZF). The experiments showed that amentoflavone did not change locomotion and did not cause toxicity in aZF during up to 96 h of analysis, with a median lethal concentration (LC50) greater than 1.0 mg/mL. The reversal of anxiety by pretreatment with granisetron suggested that the anxiolytic effect of amentoflavone is dependent on serotonergic 5-HT3A/3B receptors. Furthermore, amentoflavone reversed anxiety due to flumazenil pretreatment, suggesting a dependence on the GABAA receptor. The three concentrations of amentoflavone tested were effective in treating anxiety resulting from alcohol withdrawal. In silico analysis validated the in vivo results, supporting the idea that the interaction of amentoflavone with the protein occurs in a more stable manner than reference compounds. Amid growing interest in natural alternatives to treat anxiety disorders, amentoflavone is a potential candidate for a new anxiolytic compound that acts specifically on the 5HT3A/3B and GABAergic serotonergic pathways.
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