Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid Leukemia Using a Network Pharmacology-Based Strategy

作者：Huayao Li, Lijuan Liu, Cun Liu, Jing Zhuang, Chao Zhou, Jing Yang, Chundi Gao, Gongxi Liu, Qingliang Lv, Changgang Sun · 发表于：Medical Science Monitor · 年份：2018 · DOI：10.12659/msm.908756 · 被引用次数：30 · 研究领域：Computational Drug Discovery Methods、Synthesis and biological activity、Cytokine Signaling Pathways and Interactions

Qingdai, a traditional Chinese medicine (TCM) used for the treatment of chronic myeloid leukemia (CML) with good efficacy, has been used in China for decades. However, due to the complexity of traditional Chinese medicinal compounds, the pharmacological mechanism of Qingdai needs further research. In this study, we investigated the pharmacological mechanisms of Qingdai in the treatment of CML using network pharmacology approaches. First, components in Qingdai that were selected by pharmacokinetic profiles and biological activity predicted putative targets based on a combination of 2D and 3D similarity measures with known ligands. Then, an interaction network of Qingdai putative targets and known therapeutic targets for the treatment of chronic myeloid leukemia was constructed. By calculating the 4 topological features (degree, betweenness, closeness, and coreness) of each node in the network, we identified the candidate Qingdai targets according to their network topological importance. The composite compounds of Qingdai and the corresponding candidate major targets were further validated by a molecular docking simulation. Seven components in Qingdai were selected and 32 candidate Qingdai targets were identified; these were more frequently involved in cytokine-cytokine receptor interaction, cell cycle, p53 signaling pathway, MAPK signaling pathway, and immune system-related pathways, which all play important roles in the progression of CML. Finally, the molecular docking simul...