计算机模拟研究揭示了乌苏酸这种抗抑郁分子的多个神经靶点。
In Silico Studies Revealed Multiple Neurological Targets for the Antidepressant Molecule Ursolic Acid.
机构信息
Division of Biological Sciences and Engineering, Netaji Subhas Institute of Technology, Sector-3, Dwarka, New Delhi, 110078, India.
Federal University of Paraíba, Campus I, Joao Pessoa-PB, Brazil.
出版信息
Curr Neuropharmacol. 2017 Nov 14;15(8):1100-1106. doi: 10.2174/1570159X14666161229115508.
Abstract
BACKGROUND
Ursolic acid, a bioactive pentacyclic triterpenoid had been evaluated for its interaction with the neurological targets associated with antidepressant drugs. Current study was to mechanistically analyze the probable site of action for ursolic acid on the target proteins.
METHODS
Ursolic acid has been docked with monoamine oxidase isoforms: MAO-A and MAO-B, LeuT (homologue of SERT, NET, DAT) and Human C-terminal CAP1 using GRIP docking methodology.
RESULTS
Results revealed its non-selective antidepressant action with strong binding affinity towards LeuT and MAO-A proteins, which was found to be comparable with the reference ligands like chlorgyline, clomipramine, sertraline and deprenyl/selegiline.
CONCLUSION
Significant binding affinity of ursolic acid was seen with MAO-A, which indicated its potential role in other neurological disorders, for example, Alzheimer's disease and Parkinson disease besides depression.
摘要
背景
熊果酸是一种具有生物活性的五环三萜类化合物，已对其与抗抑郁药物相关的神经靶标相互作用进行了评估。本研究旨在从机制上分析熊果酸在靶蛋白上的可能作用部位。
方法
使用 GRIP 对接方法，将熊果酸与单胺氧化酶同工酶 MAO-A 和 MAO-B、LeuT（SERT、NET、DAT 的同源物）和人类 C 端 CAP1 对接。
结果
结果表明，它具有非选择性抗抑郁作用，对 LeuT 和 MAO-A 蛋白具有很强的结合亲和力，与参考配体如氯丙嗪、氯米帕明、舍曲林和丙炔苯丙胺/司来吉兰的亲和力相当。
结论
熊果酸与 MAO-A 具有显著的结合亲和力，这表明其在其他神经疾病（如阿尔茨海默病和帕金森病）中除了抑郁之外，还可能具有潜在作用。
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