Bhuia Md Shimul, Rokonuzzman Md, Hossain Md Imran, Ansari Siddique Akber, Ansari Irfan Aamer, Islam Tawhida, Al Hasan Md Sakib, Mubarak Mohammad S, Islam Muhammad Torequl
Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel). 2023 Sep 7;16(9):1271. doi: 10.3390/ph16091271.
Numerous previous studies reported that ferulic acid exerts anxiolytic activity. However, the mechanisms have yet to be elucidated. The current study aimed to investigate the anxiolytic effect of -ferulic acid (TFA), a stereoisomer of ferulic acid, and evaluated its underlying mechanism using in vivo and computational studies. For this, different experimental doses of TFA (25, 50, and 75 mg/kg) were administered orally to albino mice, and various behavioral methods of open field, hole board, swing box, and light-dark tests were carried out. Diazepam (DZP), a positive allosteric modulator of the GABA receptor, was employed as a positive control at a dose of 2 mg/kg, and distilled water served as a vehicle. Additionally, molecular docking was performed to estimate the binding affinities of the TFA and DZP toward the GABA receptor subunits of α2 and α3, which are associated with the anxiolytic effect; visualizations of the ligand-receptor interaction were carried out using various computational tools. Our findings indicate that TFA dose-dependently reduces the locomotor activity of the animals in comparison with the controls, calming their behaviors. In addition, TFA exerted the highest binding affinity (-5.8 kcal/mol) to the α2 subunit of the GABA receptor by forming several hydrogen and hydrophobic bonds. Taken together, our findings suggest that TFA exerts a similar effect to DZP, and the compound exerts moderate anxiolytic activity through the GABAergic interaction pathway. We suggest further clinical studies to develop TFA as a reliable anxiolytic agent.
此前众多研究报道阿魏酸具有抗焦虑活性。然而，其作用机制尚未阐明。本研究旨在探究阿魏酸的立体异构体 - 阿魏酸（TFA）的抗焦虑作用，并通过体内和计算机模拟研究评估其潜在机制。为此，将不同实验剂量的TFA（25、50和75毫克/千克）口服给予白化小鼠，并进行旷场、洞板、摇摆箱和明暗试验等多种行为学方法检测。将GABA受体的正变构调节剂地西泮（DZP）以2毫克/千克的剂量用作阳性对照，蒸馏水作为溶剂。此外，进行分子对接以估计TFA和DZP对与抗焦虑作用相关的α2和α3 GABA受体亚基的结合亲和力；使用各种计算机工具对配体 - 受体相互作用进行可视化分析。我们的研究结果表明，与对照组相比，TFA剂量依赖性地降低动物的运动活性，使它们的行为平静下来。此外，TFA通过形成多个氢键和疏水键对GABA受体的α2亚基表现出最高的结合亲和力（-5.8千卡/摩尔）。综上所述，我们的研究结果表明TFA与DZP具有相似的作用，该化合物通过GABA能相互作用途径发挥适度的抗焦虑活性。我们建议进一步开展临床研究，以将TFA开发成为一种可靠的抗焦虑药物。
