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香叶醇 - 芳樟醇联合治疗的γ-氨基丁酸能镇静前景:一项通过体内和计算机模拟研究的拮抗干预。

Gabaergic sedative prospection of sclareol-linalool co-treatment: An antagonistic intervention through in vivo and in silico studies.

作者信息

Islam Muhammad Torequl, Al Hasan Md Sakib, Ferdous Jannatul, Mia Emon, Yana Noshin Tasnim, Ansari Irfan Aamer, Ansari Siddique Akber, Islam Md Amirul, Coutinho Henrique Douglas Melo

机构信息

Pharmacy Discipline, Khulna University, Khulna 9208, Bangladesh; Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh.

Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj 8100, Bangladesh.

出版信息

Neurosci Lett. 2025 Jan 10;845:138060. doi: 10.1016/j.neulet.2024.138060. Epub 2024 Nov 23.

DOI:10.1016/j.neulet.2024.138060
PMID:39586457
Abstract

Sleep disturbance causes many health problems in humans worldwide. This study evaluated the effects and possible mechanisms of sclareol (SCL) and/or linalool (LIN) through in vivo and in silico studies. For this, young chicks SCL (5, 10, and 20 mg/kg) and/or LIN (50 mg/kg) were orally administered thirty minutes before to the thiopental sodium (TS)-induced chicks with or without the standard drug diazepam (DZP: 3 mg/kg). Incidence, onset, and duration of sleep were then noted. The results suggest that SCL dose-dependently increased the onset and decreased the duration of sleep in animals. In contrast, LIN50 significantly (p < 0.05) decreased onset and increased sleep duration. SCL20 combined with LIN50 and/or DZP3 modulated the sleep parameters in animals. In combination, LIN50 showed better effects with DZP3, where the percentage decrease in latency and increase in sleep duration were 54.20 and 168.65 %, respectively. SCL20 when combined with LIN50 + DZP3 also modulated the onset and duration of sleep in animals. Further, in silico studies suggest that SCL and LIN have binding affinities with the 6X3X protein of the GABA receptor (α1 and β2 subunits) of -6.9 and -6.8 kcal/mol, respectively. The standard drug DZP showed a binding affinity of -5.0 kcal/mol. Taken together, SCL may exert an angiogenic-like effect and antagonize LIN and/or DZP-mediated sedative effects in TS-induced chicks, possibly through the GABA receptor α1 and β2 subunits interaction pathway.

摘要

睡眠障碍在全球范围内给人类带来了诸多健康问题。本研究通过体内和计算机模拟研究评估了香紫苏醇(SCL)和/或芳樟醇(LIN)的作用及可能机制。为此,在给硫喷妥钠(TS)诱导的雏鸡口服标准药物地西泮(DZP:3mg/kg)之前或之后30分钟,给幼雏口服SCL(5、10和20mg/kg)和/或LIN(50mg/kg)。随后记录睡眠的发生率、开始时间和持续时间。结果表明,SCL剂量依赖性地增加了动物睡眠的开始时间并缩短了睡眠持续时间。相比之下,LIN50显著(p<0.05)缩短了睡眠开始时间并延长了睡眠持续时间。SCL20与LIN50和/或DZP3联合使用可调节动物的睡眠参数。联合使用时,LIN50与DZP3显示出更好的效果,其中潜伏期的百分比降低和睡眠时间的增加分别为54.20%和168.65%。SCL20与LIN50+DZP3联合使用时也调节了动物睡眠的开始时间和持续时间。此外,计算机模拟研究表明,SCL和LIN分别与GABA受体(α1和β2亚基)的6X3X蛋白具有-6.9和-6.8kcal/mol的结合亲和力。标准药物DZP的结合亲和力为-5.0kcal/mol。综上所述,SCL可能发挥类似血管生成的作用,并拮抗LIN和/或DZP在TS诱导的雏鸡中的镇静作用,可能是通过GABA受体α1和β2亚基相互作用途径。

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