Hu Shuaihang, Dan Wenchao, Liu Jinlei, Ha Peng, Zhou Tong, Guo Xinyuan, Hou Wei
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2021 Apr 1;2021:5530898. doi: 10.1155/2021/5530898. eCollection 2021.
In this study, the role of traditional Chinese medicine (TCM) in relieving epidermal growth factor receptor-tyrosine kinase inhibitor- (EGFR-TKI-) associated diarrhea was discussed by network pharmacology and data mining. Prediction of drug targets by introducing the EGFR-TKI molecular structures into the SwissTargetPrediction platform and diarrhea-related targets in the DrugBank, GeneCards, DisGeNET, and OMIM databases were obtained. Compounds in the drug-disease target intersection were screened by absorption, distribution, metabolism, and excretion parameters and Lipinski's rule in Traditional Chinese Medicine Systems Pharmacology. TCM-containing compounds were selected, and information on the property, taste, and meridian tropism of these TCMs was summarized and analyzed. A target-compound-TCM network diagram was constructed, and core targets, compounds, and TCMs were selected. The core targets and components were docked by AutoDock Vina (Version 1.1.2) to explore the target combinations of related compounds and evaluate the docking activity of related targets and compounds. Twenty-three potential therapeutic TCM targets for the treatment of EGFR-TKI-related diarrhea were obtained. There were 339 compounds acting on potential therapeutic targets, involving a total of 402 TCMs. The results of molecular docking showed good binding between the core targets and compounds, and the binding between the core targets and compounds was similar to that of the core target and the recommended drug loperamide. TCMs have multitarget characteristics and are present in a variety of compounds used for relieving EGFR-TKI-associated diarrhea. Antitumor activity and the efficacy of alleviating diarrhea are the pharmacological basis of combining TCMs with EGFR-TKI in the treatment of non-small-cell lung cancer. The core targets, compounds, and TCMs can provide data to support experimental and clinical studies on the relief of EGFR-TKI-associated diarrhea in the future.
在本研究中，通过网络药理学和数据挖掘探讨了中药在缓解表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）相关腹泻中的作用。将EGFR-TKI分子结构导入SwissTargetPrediction平台预测药物靶点，并从DrugBank、GeneCards、DisGeNET和OMIM数据库中获取腹泻相关靶点。通过中药系统药理学中的吸收、分布、代谢、排泄参数和Lipinski规则筛选药物-疾病靶点交集中的化合物。选择含中药的化合物，总结并分析这些中药的性味归经信息。构建靶点-化合物-中药网络图，筛选出核心靶点、化合物和中药。利用AutoDock Vina（版本1.1.2）对核心靶点和成分进行对接，探索相关化合物的靶点组合，评估相关靶点与化合物的对接活性。获得了23个治疗EGFR-TKI相关腹泻的潜在治疗性中药靶点。有339种化合物作用于潜在治疗靶点，涉及402种中药。分子对接结果显示核心靶点与化合物之间具有良好的结合，核心靶点与化合物之间的结合与核心靶点与推荐药物洛哌丁胺的结合相似。中药具有多靶点特性，存在于多种用于缓解EGFR-TKI相关腹泻的化合物中。抗肿瘤活性和缓解腹泻的功效是中药与EGFR-TKI联合治疗非小细胞肺癌的药理学基础。核心靶点、化合物和中药可为未来缓解EGFR-TKI相关腹泻的实验和临床研究提供数据支持。
