Akbor Md Showkot, Al Hasan Md Sakib, Haque Mst Farjanamul, Husain Zakir, Islam Md Tahajul, Hossen Md Samim, Shadin Md, Ahammed Shoyaeb, Yana Noshin Tasnim, Ansari Siddique Akber, Ansari Irfan Aamer, Islam Muhammad Torequl
Department of Pharmacy, Gopalganj Science and Technology University, Gopalganj, 8100, Bangladesh.
Bioinformatics and Drug Innovation Laboratory, BioLuster Research Center Ltd., Gopalganj, 8100, Bangladesh.
Neuromolecular Med. 2025 Jun 5;27(1):45. doi: 10.1007/s12017-025-08839-z.
The bisbenzylisoquinoline alkaloid dauricine (DAU) is known for its neuroprotective effects in animals. This study investigates the memory-enhancing effects of DAU in Swiss albino mice using both in vivo and in silico approaches, focusing on its interaction with the D2 dopamine (DOP) receptor. Behavioral tests, including marble burying, dust removal, and trained swimming, were used to assess cognitive performance, anxiety, and motor coordination. Molecular docking studies revealed that DAU binds strongly to the D2 DOP receptor (6CM4 protein), with a binding affinity of - 7.9 kcal/mol, forming significant hydrogen and hydrophobic bonds. Additionally, the pharmacokinetics and toxicity profiles of DAU were also evaluated. In vivo results showed that DAU improved behavioral performance in a dose-dependent manner, with the DAU-10 group showing significant (p < 0.05) enhancement compared to the control and standard groups. The DAU-10 + DOP-22 combination group also showed remarkable results compared to the standard alone. Pharmacokinetics and toxicity profiles were also assessed, revealing favorable properties but some concerns regarding mutagenicity and immunotoxicity. These findings suggest that DAU, especially when combined with D2 DOP receptor agonists, holds significant potential for memory enhancement and warrants further investigation.
双苄基异喹啉生物碱蝙蝠葛碱(DAU)以其在动物体内的神经保护作用而闻名。本研究使用体内和计算机模拟方法,研究DAU对瑞士白化小鼠记忆增强的作用,重点关注其与D2多巴胺(DOP)受体的相互作用。行为测试,包括埋大理石、除尘和训练游泳,用于评估认知能力、焦虑和运动协调性。分子对接研究表明,DAU与D2 DOP受体(6CM4蛋白)强烈结合,结合亲和力为-7.9千卡/摩尔,形成显著的氢键和疏水键。此外,还评估了DAU的药代动力学和毒性特征。体内结果表明,DAU以剂量依赖的方式改善行为表现,与对照组和标准组相比,DAU-10组表现出显著(p<0.05)的增强。与单独使用标准药物相比,DAU-10+DOP-22联合组也显示出显著效果。还评估了药代动力学和毒性特征,结果显示其具有良好的特性,但对致突变性和免疫毒性存在一些担忧。这些发现表明,DAU,尤其是与D2 DOP受体激动剂联合使用时,在增强记忆方面具有巨大潜力,值得进一步研究。
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