Al Hasan Md Sakib, Bhuia Md Shimul, Sheikh Salehin, Bithi Sumaya Akter, Saim Md Abu, Kamli Hossam, Ansari Siddique Akber, Ahammed Nowreen Tabassum, Islam Muhammad Torequl
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, Dhaka, Bangladesh.
Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj, 8100, Dhaka, Bangladesh.
Sleep Med. 2025 Feb;126:88-96. doi: 10.1016/j.sleep.2024.12.007. Epub 2024 Dec 8.
The purpose of this study was to investigate the sedative effects of Chrysin (CHR) along with modulatory effects on diazepam (DZP) and flumazenil (FLU) in an animal sleep model produced by thiopental sodium (TS). Additionally, we explored the pharmacokinetics and potential GABA receptor interactions of CHR through computational studies. Swiss albino mice were treated with intraperitoneal administration of CHR (5 and 10 mg/kg), DZP (2 mg/kg), and FLU (0.1 mg/kg) either alone or in combination. Sleeping onset and duration were measured following TS administration. Molecular docking was performed to investigate CHR's binding affinity with GABA (PDB: 6X3X) receptors. Results found that CHR significantly (p < 0.05) reduced sleep latency and increased sleep duration in a dose-dependent manner compared to the control group. The highest dose (CHR-10) exhibited the most potent significant sedative effect with onset (11.57 ± 1.74 min) and duration (172.86 ± 7.37 min). Combination therapy of CHR-10 with DZP resulted in synergistic effects, further enhancing sleep duration. In molecular docking, CHR demonstrated a higher binding affinity (-8.9 kcal/mol) for GABA receptors compared to DZP (-8.7 kcal/mol) and FLU (-6.6 kcal/mol). CHR also showed favorable pharmacokinetic properties with high intestinal absorption and low toxicity. CHR exhibits promising sedative activity, with the potential to enhance the effects of traditional sedatives like DZP. However, further research, including clinical trials and detailed mechanistic studies, is warranted to explore its full therapeutic potential.
本研究的目的是在硫喷妥钠（TS）诱导的动物睡眠模型中，研究白杨素（CHR）的镇静作用以及对地西泮（DZP）和氟马西尼（FLU）的调节作用。此外，我们通过计算研究探索了CHR的药代动力学和潜在的GABA受体相互作用。将瑞士白化小鼠通过腹腔注射单独或联合给予CHR（5和10mg/kg）、DZP（2mg/kg）和FLU（0.1mg/kg）。在给予TS后测量入睡时间和睡眠时间。进行分子对接以研究CHR与GABA（PDB：6X3X）受体的结合亲和力。结果发现，与对照组相比，CHR以剂量依赖性方式显著（p<0.05）缩短睡眠潜伏期并延长睡眠时间。最高剂量（CHR-10）表现出最有效的显著镇静作用，起效时间为（11.57±1.74分钟），持续时间为（172.86±7.37分钟）。CHR-10与DZP联合治疗产生协同作用，进一步延长睡眠时间。在分子对接中，CHR对GABA受体的结合亲和力（-8.9kcal/mol）高于DZP（-8.7kcal/mol）和FLU（-6.6kcal/mol）。CHR还表现出良好的药代动力学特性，肠道吸收高且毒性低。CHR具有有前景的镇静活性，有可能增强像DZP这样的传统镇静剂的效果。然而，需要进一步的研究，包括临床试验和详细的机制研究，以探索其全部治疗潜力。
