阿尔茨海默病(AD)是痴呆最常见的神经退行性疾病,占所有病例的70%以上。尽管大量报道了曼陀罗(DI)及其植物化学成分在AD治疗中的实验研究,目前迫切需要阐明AD的多机制和多水平治疗原则。在这项研究中,分子对接和网络药理学用于评估DI治疗AD的活性化合物和分子靶标。DI的植物化学化合物是从印度药用植物获得的,植物化学,和治疗学(IMPPAT)以及中药系统药理学(TCMSP)数据库。筛选包括DI的28种最丰富的组分,并且使用瑞士目标预测数据库来预测这些化合物的目标。GeneCards数据库用于收集AD相关基因。DI和AD目标都被导入到维恩图中,28个重叠基因被鉴定为潜在的DI抗AD靶标。结果表明,毒素B,二甲苯胺,蹦床,Tropic酸对AD相关基因无影响。此外,GO富集分析表明,DI影响分子功能和生物过程,如学习或记忆和化学突触传递的调节以及膜移植物和膜微域。KEGG通路分析显示,与DI抗AD作用有关的关键通路包括5-羟色胺能突触,IL-17信号通路,和AGE-RAGE信号通路在糖尿病并发症中的作用。基于STRING和Cytoscape网络分析平台,十大抗AD核心目标包括APP,CAS3,IL6,BACE1,IL1B,ACE,PSEN1,GAPDH,GSK3B和ACHE。前两种分子与前三种靶蛋白的分子对接和分子动力学模拟证实了对接位点处的强结合亲和力和稳定性。总的来说,我们的发现为进一步研究DI潜在抗AD药物的开发和优化铺平了道路.由RamaswamyH.Sarma沟通。
Alzheimer\'s disease (AD) ranks as the most prevalent neurodegenerative disorder with dementia and it accounts for more than 70% of all cases. Despite extensive reporting on the experimental investigation of Datura innoxia (DI) and its phytochemical components in the treatment of AD, the urgent need for elucidation of the principle of multi-mechanism and multi-level treatment of AD remains. In this research, molecular docking and network pharmacology were used to evaluate active compounds and molecular targets of DI for the treatment of AD. The phytochemical compounds of DI were obtained from the Indian Medicinal Plants, Phytochemistry, and Therapeutics (IMPPAT) as well as the Traditional Chinese Medicine System Pharmacology (TCMSP) databases. The screening includes the 28 most abundant components of DI and the Swiss Target Prediction database was used to predict targets of these compounds. The GeneCards database was used to collect AD-related genes. Both DI and AD targets were imported into a Venn diagram, and the 28 overlapped genes were identified as potential DI anti-AD targets. The results showed that Dinoxin B, Meteloidine, Scopoline, and Tropic acid had no effect on AD-related genes. Furthermore, the GO enrichment analysis indicates that DI influences molecular functions and biological processes such as learning or memory and modulation of chemical synaptic transmission as well as the membrane raft and membrane microdomain. The KEGG pathway analysis revealed that the key pathways implicated in DI\'s anti-AD actions include serotonergic synapse, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Based on the
STRING and Cytoscape network-analysis platforms, the top ten anti-AD core targets include APP, CASP3, IL6, BACE1, IL1B, ACE, PSEN1, GAPDH, GSK3B and ACHE. The molecular docking and molecular dynamic simulation of the top two molecules against the top three target proteins confirmed the strong binding affinity and stability at the docked site. Overall, our findings pave the path for further research into the development and optimization of potential anti-AD agents from DI.Communicated by Ramaswamy H. Sarma.