药学学报, 2022, 57(5): 1387-1395
引用本文:
吕雪琪, 郭聪聪, 许悦, 靳香菊, 王映红*. 基于代谢组学和网络药理学方法探讨芪参益气滴丸改善心衰大鼠心脏能量代谢的作用机制[J]. 药学学报, 2022, 57(5): 1387-1395.
LÜ Xue-qi, GUO Cong-cong, XU Yue, JIN Xiang-ju, WANG Ying-hong*. A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology[J]. Acta Pharmaceutica Sinica, 2022, 57(5): 1387-1395.

基于代谢组学和网络药理学方法探讨芪参益气滴丸改善心衰大鼠心脏能量代谢的作用机制
吕雪琪, 郭聪聪, 许悦, 靳香菊, 王映红*
中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
摘要:
组学与生物信息学为中药机制研究带来了新的思路。本研究采用代谢组学和网络药理学联合策略探讨芪参益气滴丸(Qishen Yiqi dropping pill,QDP)改善心力衰竭(heart failure,HF)大鼠心脏能量代谢的药效物质基础及网络调控机制。1H NMR代谢组学分析从HF大鼠心脏组织中发现肉碱、谷氨酰胺、肌酸、脯氨酸、高瓜氨酸、乳酸、牛磺酸和丙氨酸等8个代谢物在QDP治疗后显著回调,表明QDP调控糖、脂、ATP和蛋白质代谢等过程。动物实验操作均遵循中国医学科学院药物研究所实验动物管理与动物福利伦理委员会的规定。利用网络药理学建立“药物-成分-靶点-疾病”网络,并结合代谢组学结果提取与上述代谢过程相关的“成分-靶点”子网络,显示了QDP调节能量代谢潜在的47个作用靶点和79个化学成分,提炼了熊果酸、三七皂苷、人参皂苷等关键化学成分与INS、PPARG、AKT1等核心靶点,同时也从能量代谢的角度展示了QDP与HF之间多靶点、多成分的复杂作用关系。分子对接技术验证了部分靶点与化学成分良好的相互作用,其结合能均小于-5 kcal·mol-1。本研究结果为QDP临床应用及方剂开发利用提供了有用信息。
关键词:    芪参益气滴丸      心力衰竭      代谢组学      网络药理学      分子对接     
A proposed mechanism by which Qishen Yiqi dropping pill improves cardiac energy metabolism in rats with heart failure based on metabolomics and network pharmacology
LÜ Xue-qi, GUO Cong-cong, XU Yue, JIN Xiang-ju, WANG Ying-hong*
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
“Omics” and bioinformatics have brought new ideas to the study of traditional Chinese medicine. This study used metabonomics and network pharmacology to investigate the pharmacodynamic basis and regulation of Qishen Yiqi dropping pill (QDP) improving cardiac energy metabolism in rats with heart failure (HF). 1H NMR metabonomics analysis showed that eight metabolites, including carnitine, glutamine, creatine, proline, homocitrulline, lactic acid, taurine and alanine appeared significant callback after QDP treatment for HF. The results indicate that QDP regulates the metabolism of carbohydrate, lipid, ATP and protein. The animal experiment was conducted in accordance with the regulations of the Ethics Committee for Experimental Animal Management and Animal Welfare of Institute of Materia Medica, Chinese Academy of Medical Sciences. A "drug-component-target-disease" network was established using network pharmacology, and the "component-target" sub-network related to the above energy metabolism processes was extracted by combining metabonomics results. Results revealed 79 chemical compounds and 47 potential targets of QDP involved in the regulation of energy metabolism, and identified key chemical components including ursolic acid, notoginsenoside G, ginsenoside-Rh1, and core targets such as INS, PPARG, and AKT1. The results also demonstrated the complex multi-target and multi-component relationship between QDP and HF from the perspective of energy metabolism. The molecular docking technique verified a strong interaction between some targets and chemical compounds, with affinities less than -5 kcal·mol-1. The results of this study provide useful information for the clinical application, development, and utilization of QDP.
Key words:    Qishen Yiqi dropping pill    heart failure    metabonomics    network pharmacology    molecular docking   
收稿日期: 2022-01-18
DOI: 10.16438/j.0513-4870.2022-0092
基金项目: 国家科技重大专项项目(2018ZX09711001-002-004);中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-009).
通讯作者: 王映红,Tel:86-10-63165216,E-mail:wyh@imm.ac.cn
Email: wyh@imm.ac.cn
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