Liu Shengwei, He Cui, Liao Yuan, Liu Hailin, Mao Wanli, Shen Zhengze
Department of Pharmacy, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China.
Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
Evid Based Complement Alternat Med. 2020 Jun 25;2020:6317230. doi: 10.1155/2020/6317230. eCollection 2020.
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.
Sixty-eight active ingredients with suitable pharmacokinetic profiles and biological activities were selected through ADME screening . 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.
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.
在本研究中，采用基于系统药理学的策略来阐明石菖蒲和党参治疗阿尔茨海默病（AD）的协同机制。这个新型的系统药理学模型由成分信息、药代动力学分析和药理学数据组成。此外，利用京都基因与基因组百科全书（KEGG）数据库对相关通路进行了压缩，并在BioGPS库中确定了器官分布。
通过ADME筛选，选择了68种具有合适药代动力学特征和生物活性的活性成分。基于APP、CHRM1和PTGS1等62个与AD相关的靶点，系统分析表明这两种草药主要参与PI3K-Akt信号通路、MAPK信号通路、神经活性配体-受体相互作用以及流体剪切力与动脉粥样硬化，表明它们对AD具有协同作用。然而，石菖蒲作用于KDR基因，而党参作用于IGF1R、MET、IL1B和CHUK，表明它们对AD也具有互补作用。成分贡献得分涉及29种成分，它们对该配方治疗AD的总贡献得分的贡献为90.14%，这强调了这些草药对AD的有效治疗作用源自石菖蒲和党参两者，而非单一草药。器官分布表明活性成分的靶点主要位于全血、大脑和肌肉中，这些都与AD相关。
总之，我们的研究结果表明，系统药理学方法成功揭示了石菖蒲和党参治疗AD的协同和互补机制。
