Jatamansinol from <i>Nardostachys jatamansi</i>: a multi-targeted neuroprotective agent for Alzheimer’s disease

Alzheimer’s disease (AD) is a multifactorial progressive and irreversible neurodegenerative disorder characterized by severe memory impairment and cognitive disability in the middle and old-aged human population. There are no proven drugs for AD treatment and prevention. In Ayurveda, medhya plants are used to prepare Rasayana, and its consumption improves memory and cognition. <i>Nardostachys jatamansi</i> (D.Don) DC is a medhya plant used in traditional medicine to treat neurological disorders, and its unique pyranocoumarins can be a potential drug candidate for AD. Given its traditional claims, this study aims to find the multi-target potential efficacy of the ligands (drug molecules) against the AD from <i>N. jatamansi</i> pyranocoumarins using computational drug discovery techniques. Drug likeliness analysis confirms that pyranocoumarins of <i>N. jatamansi,</i> such as seselin, jatamansinol, jatamansine, jatamansinone, and dihydrojatamansin are probable drug candidates for AD. Molecular docking, molecular dynamic simulations, and Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis confirm that dihydrojatamansin inhibits acetylcholinesterase (<i>AChE</i>), and jatamansinol inhibits butyrylcholinesterase (<i>BuChE</i>), glycogen synthase kinase 3β <i>(GSK3β</i>), and kelch-like ECH-associating protein 1 (<i>Keap1</i>) AD therapeutic targets. Therefore, this study provides potential multi-target inhibitors that would further validate experimental studies, leading to new treatments for AD. Communicated by Ramaswamy H. Sarma阿尔茨海默病（Alzheimer’s disease, AD）是一种多因素参与的进行性、不可逆神经退行性疾病，以中老年群体出现严重记忆障碍与认知功能缺损为特征。目前尚无经临床证实有效的AD治疗与预防药物。在阿育吠陀（Ayurveda）医学体系中，益智类植物（medhya plants）被用于制备拉沙亚那（Rasayana）方剂，服用该方剂可改善记忆与认知功能。甘松（Nardostachys jatamansi (D.Don) DC）属于益智类植物，在传统医学中用于治疗神经系统疾病，其独特的吡喃香豆素类（pyranocoumarins）成分有望成为AD的潜在药物候选分子。鉴于其传统药用价值，本研究旨在利用计算药物发现技术，探究甘松吡喃香豆素类成分中的配体（药物分子）对抗AD的多靶点潜在药效。药物相似性分析结果显示，甘松中的吡喃香豆素类成分，如邪蒿素（seselin）、甘松醇（jatamansinol）、甘松碱（jatamansine）、甘松酮（jatamansinone）以及二氢甘松素（dihydrojatamansin），均为潜在的AD治疗药物候选分子。分子对接、分子动力学模拟以及分子力学/广义玻恩表面积（Molecular Mechanics/Generalized Born Surface Area, MM-GBSA）分析结果显示：二氢甘松素可抑制乙酰胆碱酯酶（acetylcholinesterase, AChE），而甘松醇可抑制丁酰胆碱酯酶（butyrylcholinesterase, BuChE）、糖原合成激酶3β（glycogen synthase kinase 3β, GSK3β）以及Kelch样ECH相关蛋白1（kelch-like ECH-associating protein 1, Keap1）这些AD治疗靶点。因此，本研究筛选得到了具有潜力的多靶点抑制剂，可为后续实验验证提供依据，进而推动AD新型治疗方案的开发。本文由Ramaswamy H. Sarma转达

搜集汇总

背景与挑战

背景概述

该数据集是关于从Nardostachys jatamansi植物中提取的Jatamansinol作为阿尔茨海默病多靶点神经保护剂的研究补充材料。数据集包含计算药物发现分析结果，确认了吡喃香豆素类化合物（如dihydrojatamansin和jatamansinol）对乙酰胆碱酯酶、丁酰胆碱酯酶等关键靶点的抑制作用，为阿尔茨海默病的实验研究提供潜在多靶点抑制剂数据。