Anxiogenic-like effects of coumarin, possibly through the GABAkine interaction pathway: Animal studies with in silico approaches.

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2024-12-10 DOI:10.1016/j.bbr.2024.115392

Abdullah Al Shamsh Prottay, Emamuzzaman, Tawfik Rakaiyat Ripu, Md Nazim Sarwar, Towfiqur Rahman, Md Shakil Ahmmed, Mehedi Hasan Bappi, Md Emon, Siddique Akber Ansari, Henrique D M Coutinho, Muhammad Torequl Islam

{"title":"Anxiogenic-like effects of coumarin, possibly through the GABAkine interaction pathway: Animal studies with in silico approaches.","authors":"Abdullah Al Shamsh Prottay, Emamuzzaman, Tawfik Rakaiyat Ripu, Md Nazim Sarwar, Towfiqur Rahman, Md Shakil Ahmmed, Mehedi Hasan Bappi, Md Emon, Siddique Akber Ansari, Henrique D M Coutinho, Muhammad Torequl Islam","doi":"10.1016/j.bbr.2024.115392","DOIUrl":null,"url":null,"abstract":"Background: Anxiety disorder is the most common mental illness and a major contributor to impairment. Thus, there is an urgent need to find novel lead compounds to mitigate anxiety. It is widely recognized that the neurobiology of anxiety-related behavior involves GABAergic systems.Objectives: This research aimed to examine the anxiogenic action of coumarin (CMN), a natural benzopyrone derived from plants, and determine its underlying mechanism through in vivo and in silico investigations.Methods: This was accomplished by using a variety of behavioral procedures, including open field, swing, hole cross, and light-dark tests, on male and female Swiss albino mice that had been orally administered three experimental doses of CMN (1, 2, and 4 mg/kg). The CMN group was also examined with the GABAA receptor agonist diazepam (DZP, 2 mg/kg) and flumazenil antagonist (FLU, 0.1 mg/kg). Furthermore, CMN and standards were subjected to a molecular docking analysis to determine their binding affinities for the GABAA receptor subunits (α1, α4, β2, γ2, and δ). Several software programs were used to visualize the ligand-receptor interaction and analyze the pharmacokinetic profile.Results: Compared to typical treatments, our results show that CMN (1 mg/kg) significantly (p < 0.05) increases the locomotor activity of animals. Furthermore, CMN exerted the highest binding affinity (-6.5 kcal/mol) with the GABA-α1 receptor compared to conventional DZP. Along with FLU, CMN displayed several hydrophobic and hydrogen bonds with GABAA receptor subunits. The pharmacokinetic and drug-like properties of CMN are also remarkable. In animal studies, CMN worked synergistically with FLU to provide anxiogenic-like effects.Conclusion: We conclude that, based on in vivo and in silico data, CMN, alone or in combination with FLU, may be employed in future neurological clinical studies. However, further research is needed to confirm this behavioral activity and elucidate the possible mechanism of action.","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":" ","pages":"115392"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Behavioural Brain Research","FirstCategoryId":"102","ListUrlMain":"https://doi.org/10.1016/j.bbr.2024.115392","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Anxiety disorder is the most common mental illness and a major contributor to impairment. Thus, there is an urgent need to find novel lead compounds to mitigate anxiety. It is widely recognized that the neurobiology of anxiety-related behavior involves GABAergic systems.

Objectives: This research aimed to examine the anxiogenic action of coumarin (CMN), a natural benzopyrone derived from plants, and determine its underlying mechanism through in vivo and in silico investigations.

Methods: This was accomplished by using a variety of behavioral procedures, including open field, swing, hole cross, and light-dark tests, on male and female Swiss albino mice that had been orally administered three experimental doses of CMN (1, 2, and 4 mg/kg). The CMN group was also examined with the GABA_A receptor agonist diazepam (DZP, 2 mg/kg) and flumazenil antagonist (FLU, 0.1 mg/kg). Furthermore, CMN and standards were subjected to a molecular docking analysis to determine their binding affinities for the GABA_A receptor subunits (α1, α4, β2, γ2, and δ). Several software programs were used to visualize the ligand-receptor interaction and analyze the pharmacokinetic profile.

Results: Compared to typical treatments, our results show that CMN (1 mg/kg) significantly (p < 0.05) increases the locomotor activity of animals. Furthermore, CMN exerted the highest binding affinity (-6.5 kcal/mol) with the GABA-α1 receptor compared to conventional DZP. Along with FLU, CMN displayed several hydrophobic and hydrogen bonds with GABA_A receptor subunits. The pharmacokinetic and drug-like properties of CMN are also remarkable. In animal studies, CMN worked synergistically with FLU to provide anxiogenic-like effects.

Conclusion: We conclude that, based on in vivo and in silico data, CMN, alone or in combination with FLU, may be employed in future neurological clinical studies. However, further research is needed to confirm this behavioral activity and elucidate the possible mechanism of action.

查看原文本刊更多论文

背景介绍焦虑症是最常见的精神疾病，也是导致机体损伤的一个主要因素。因此，迫切需要找到新型先导化合物来缓解焦虑。人们普遍认为，焦虑相关行为的神经生物学涉及 GABA 能系统：本研究旨在研究香豆素（CMN）的致焦虑作用，这是一种从植物中提取的天然苯并吡喃酮，并通过体内和硅学研究确定其潜在机制：方法：对口服了三种实验剂量（1、2 和 4 毫克/千克）香豆素的雌雄瑞士白化小鼠进行了多种行为测试，包括开阔地测试、摇摆测试、孔交叉测试和光-暗测试。CMN 组还接受了 GABAA 受体激动剂地西泮（DZP-2 毫克/千克）和氟马西尼拮抗剂（FLU-0.1 毫克/千克）的检测。此外，还对 CMN 和标准品进行了分子对接分析，以确定它们与 GABAA 受体亚基（α1、α4、β2、γ2 和 δ）的结合亲和力。我们使用了几种软件对配体与受体的相互作用进行了可视化，并分析了药代动力学特征：结果：与典型的治疗方法相比，我们的研究结果表明，CMN（1 毫克/千克）能显著增加 pA 受体亚基。CMN 的药代动力学和类药物特性也非常显著。在动物实验中，CMN与FLU协同作用，产生类似焦虑的效果：我们的结论是，根据体内和硅学数据，CMN 可单独或与 FLU 联用，用于未来的神经系统临床研究。然而，还需要进一步的研究来证实这种行为活性并阐明其可能的作用机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.