Don Bosco Reiya Bosco, Selvan Christyraj Johnson Retnaraj Samuel, Yesudhason Beryl Vedha
Regeneration and Stem Cell Biology Lab, Centre for Molecular and Nanomedical Sciences, International Research Centre, Sathyabama Institute of Science and Technology, Chennai, India.
J Alzheimers Dis Rep. 2024 Dec 23;8(1):1745-1762. doi: 10.1177/25424823241307019. eCollection 2024.
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, , , , and are traditionally utilized for their memory-enhancing properties.
We computationally investigated the therapeutic potential of four nootropic herbs by uncovering the molecular mechanisms underlying their treatment for AD.
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.
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.
Herbal medicines can synergistically stimulate multiple protein targets, rendering a holistic and integrative treatment, encouraging a promising avenue to treat AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，影响着超过5500万人，而找到治愈方法仍然令人沮丧。印度草药，特别是 、 、 、 和 ，传统上因其增强记忆力的特性而被使用。
我们通过揭示四种益智草药治疗AD的分子机制，对其治疗潜力进行了计算研究。
进行了化学信息学、药代动力学和系统药理学研究，以预测植物化合物的类药物性质、蛋白质靶点、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。对AD大脑海马体和内嗅皮质中蛋白质靶点的表达进行了研究。构建网络以描绘植物化合物、药物和分子靶点之间的相互作用。
通过比较分析，我们发现植物化合物与FDA药物和临床试验中的药物有共同靶点。我们确定了潜在的活性化合物，特别是Withaferin A、Withanolide-D、Withanolide-E、Withanolide-G和Humulene epoxide II，它们可以对抗AD。有趣的是，所鉴定药物的酶抑制分数远高于FDA批准的药物。此外，调节蛋白如AβPP、乙酰胆碱酯酶、BACE1和PTPN1分别是8、16、9和22种植物化合物的靶点。尽管如此，AR和CYP19A是大多数植物化合物的主要靶点。
草药可以协同刺激多个蛋白质靶点，提供整体综合治疗，为治疗AD开辟了一条有前景的途径。
