Synergistic activity of nootropic herbs as potent therapeutics for Alzheimer's disease: A cheminformatics, pharmacokinetics, and system pharmacology approach.

IF 2.8 Q2 NEUROSCIENCES
Journal of Alzheimer's disease reports Pub Date : 2024-12-23 eCollection Date: 2024-01-01 DOI:10.1177/25424823241307019
Reiya Bosco Don Bosco, Johnson Retnaraj Samuel Selvan Christyraj, Beryl Vedha Yesudhason
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引用次数: 0

Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which subdues over 55 million people and finding a cure, still remains disenchanting. Indian medicinal herbs notably, Withania somnifera, Bacopa monnieri, Curcuma longa, and Clitoria ternatea are traditionally utilized for their memory-enhancing properties.

Objective: We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.

Methods: Cheminformatics, pharmacokinetics, and system pharmacology studies were carried out to predict the phytocompounds drug-like properties, protein targets, targets functional association and enrichment analysis. A comparative study was performed with phytocompounds and FDA-approved drugs. Investigation on the expression of protein targets in the hippocampus and entorhinal cortex of the AD brain was performed. Network was constructed to depict the interaction between phytocompounds, drugs, and molecular targets.

Results: Through comparative analysis, we found that the phytocompounds shared common targets with both FDA drugs and drugs under clinical trials. We identified potential active compounds notably, Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G, and Humulene epoxide II, that can combat AD. Interestingly, the enzyme inhibition scores of the identified drugs were much higher than FDA-approved drugs. In addition, regulatory proteins such as AβPP, acetylcholinesterase, BACE1, and PTPN1 were the targets of 8, 16, 9, and 22 phytocompounds, respectively. Nonetheless, AR and CYP19A, were the primary targets of most phytocompounds.

Conclusions: Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.

促智草药作为阿尔茨海默病有效治疗药物的协同作用:化学信息学、药代动力学和系统药理学方法。
背景:阿尔茨海默病(AD)是一种进行性神经退行性疾病,超过5500万人患有此病,目前仍未找到治愈方法。印度草药,特别是Withania somnifera,假马齿苋,姜黄,和阴蒂,传统上被用于增强记忆的特性。目的:通过揭示四种益智中药治疗AD的分子机制,对其治疗潜力进行计算研究。方法:通过化学信息学、药代动力学和系统药理学研究,预测植物化合物的类药物特性、蛋白靶点、靶点功能关联和富集分析。对植物化合物和fda批准的药物进行了比较研究。研究了AD脑海马和内嗅皮层蛋白靶点的表达。构建了描述植物化合物、药物和分子靶点之间相互作用的网络。结果:通过对比分析,我们发现植物化合物与FDA药物和临床试验药物具有共同的靶点。我们发现了潜在的活性化合物,特别是Withaferin A, Withanolide-D, Withanolide-E, Withanolide-G和Humulene环氧化物II,可以对抗AD。有趣的是,鉴定药物的酶抑制得分远高于fda批准的药物。此外,a - β pp、乙酰胆碱酯酶、BACE1和PTPN1等调节蛋白分别是8、16、9和22种植物化合物的靶点。然而,AR和CYP19A是大多数植物化合物的主要靶点。结论:草药可以协同刺激多种蛋白质靶点,提供整体和综合治疗,为治疗阿尔茨海默病提供了一条有希望的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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