Enhancing and Complementary Mechanisms of Synergistic Action of Acori Tatarinowii Rhizoma and Codonopsis Radix for Alzheimer's Disease Based on Systems Pharmacology
Enhancing and Complementary Mechanisms of Synergistic Action of Acori Tatarinowii Rhizoma and Codonopsis Radix for Alzheimer's Disease Based on Systems Pharmacology
复制标题
基于系统药理学探讨石菖蒲和党参协同治疗阿尔茨海默病的增强和互补机制
DOI：
10.1155/2020/6317230
复制
发表时间：
2020-06-25
影响因子：
--
通讯作者：
Shen, Zhengze
中科院分区：
文献类型：
--
作者：
Liu, Shengwei;He, Cui;Shen, Zhengze
材料与方法本研究采用系统药理学的方法，探讨石菖蒲和黄芪治疗AD的协同作用机制。这种新的系统药理学模型包括组分信息、药代动力学分析和药理学数据。此外，使用京都基因和基因组百科全书（KEGG）数据库压缩相关途径，并在BioGPS库中确定器官分布。结果通过计算机ADME筛选，筛选出68个药代动力学特征和生物学活性较好的活性成分。基于APP、CHRM 1、PTGS 1等62个AD相关靶点，系统分析表明，两药主要参与PI 3 K-Akt信号通路、MAPK信号通路、神经活性配体-受体相互作用、流体切应力和动脉粥样硬化，提示二者对AD具有协同作用。然而，ATR作用于KDR基因，而CR作用于IGF 1 R、MET、IL 1B和CHUK，表明它们对AD也具有互补作用。成分贡献分涉及29种成分，占本方治疗AD的总贡献分的90.14%，强调了这些药物对AD的有效治疗作用来自ATR和CR，而不是单一药物;器官分布显示有效成分的靶点主要位于全血、脑和肌肉，与AD相关的疾病。结论系统药理学方法成功揭示了ATR和CR治疗AD的协同和互补机制。
Materials and Methods In this study, a systems pharmacology-based strategy was used to elucidate the synergistic mechanism of Acori Tatarinowii Rhizoma and Codonopsis Radix for the treatment of AD. This novel systems pharmacology model consisted of component information, pharmacokinetic analysis, and pharmacological data. Additionally, the related pathways were compressed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the organ distributions were determined in the BioGPS bank. Results Sixty-eight active ingredients with suitable pharmacokinetic profiles and biological activities were selected through ADME screening in silico. Based on 62 AD-related targets, such as APP, CHRM1, and PTGS1, systematic analysis showed that these two herbs were mainly involved in the PI3K-Akt signaling pathway, MAPK signaling pathway, neuroactive ligand-receptor interaction, and fluid shear stress and atherosclerosis, indicating that they had a synergistic effect on AD. However, ATR acted on the KDR gene, while CR acted on IGF1R, MET, IL1B, and CHUK, showing that they also had complementary effects on AD. The ingredient contribution score involved 29 ingredients contributing 90.14% of the total contribution score of this formula for AD treatment, which emphasized that the effective therapeutic effects of these herbs for AD were derived from both ATR and CR, not a single herb. Organ distribution showed that the targets of the active ingredients were mainly located in the whole blood, the brain, and the muscle, which are associated with AD. Conclusions In sum, our findings suggest that the systems pharmacology methods successfully revealed the synergistic and complementary mechanisms of ATR and CR for the treatment of AD.