Anxiolytic Efficacy of Indirubin: In Vivo Approach Along with Receptor Binding Profiling and Molecular Interaction with GABAergic Pathways.

IF 2.5 4区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Ishrat Jahan Disha, Rubel Hasan, Shimul Bhuia, Siddique Akber Ansari, Irfan Aamer Ansari, Muhammad Torequl Islam
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引用次数: 0

Abstract

Anxiety is a natural response to stress, characterized by feelings of worry, fear, or unease. The current research was conducted to investigate the anxiolytic effect of indirubin (IND) in different behavioral paradigms in Swiss albino mice. To observe the animal's behavioural response to assess anxiolytic activity, different tests were performed, such as the open-field (square cross, grooming, and rearing), swing, dark-light, and hole cross tests. The experimental mice were administered IND (5 and 10 mg/kg, p.o.), where diazepam (DZP) and vehicle were used as positive and negative controls, respectively. In addition, a combination treatment (DZP+IND-10) was provided to the animals to determine the modulatory effect of IND on DZP. Molecular docking approach was also conducted to determine the binding energy of IND with the GABAA receptor (α2 and α3 subunits) and pharmacokinetics were also estimated. The findings revealed that IND dose-dependently significantly (p<0.05) reduced the animal's movement exerting calming behavior like DZP. IND also demonstrated the highest docking score (-7.7 kcal/mol) against the α3 subunit, while DZP showed a lower docking value (-6.4 kcal/mol) than IND. The ADMET analysis revealed that IND has proper drug-likeness and pharmacokinetic characteristics. In conclusion, IND exerted anxiolytic effects through GABAergic Pathways.

吲哚鲁宾的抗焦虑功效:体内方法以及受体结合分析和与 GABA 能通路的分子相互作用。
焦虑是对压力的一种自然反应,表现为担心、恐惧或不安。目前的研究旨在调查靛蓝(IND)在瑞士白化小鼠不同行为范式中的抗焦虑作用。为了观察动物的行为反应以评估抗焦虑活性,研究人员进行了不同的试验,如开场试验(方格交叉、梳理和饲养)、摇摆试验、暗光试验和洞口交叉试验。给实验小鼠注射 IND(5 和 10 mg/kg,p.o.),地西泮(DZP)和车辆分别作为阳性和阴性对照。此外,还对动物进行了联合治疗(DZP+IND-10),以确定IND对DZP的调节作用。研究人员还采用分子对接法确定了IND与GABAA受体(α2和α3亚基)的结合能,并对药代动力学进行了估算。研究结果表明,IND 与 GABAA 受体(α2 和α3 亚基)的结合能量与药代动力学有显著的剂量依赖性(p
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来源期刊
ChemistryOpen
ChemistryOpen CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.80
自引率
4.30%
发文量
143
审稿时长
1 months
期刊介绍: ChemistryOpen is a multidisciplinary, gold-road open-access, international forum for the publication of outstanding Reviews, Full Papers, and Communications from all areas of chemistry and related fields. It is co-owned by 16 continental European Chemical Societies, who have banded together in the alliance called ChemPubSoc Europe for the purpose of publishing high-quality journals in the field of chemistry and its border disciplines. As some of the governments of the countries represented in ChemPubSoc Europe have strongly recommended that the research conducted with their funding is freely accessible for all readers (Open Access), ChemPubSoc Europe was concerned that no journal for which the ethical standards were monitored by a chemical society was available for such papers. ChemistryOpen fills this gap.
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