药学学报, 2018, 53(10): 1670-1679
引用本文:
李建良, 梁慧, 蔡淑珍, 李志勇, 图雅. 基于网络药理学探讨蒙药诃子解草乌心脏毒的机制研究[J]. 药学学报, 2018, 53(10): 1670-1679.
LI Jian-liang, LIANG Hui, CAI Shu-zhen, LI Zhi-yong, TU Ya. Mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity based on network pharmacology[J]. Acta Pharmaceutica Sinica, 2018, 53(10): 1670-1679.

基于网络药理学探讨蒙药诃子解草乌心脏毒的机制研究
李建良1, 梁慧2, 蔡淑珍3, 李志勇4, 图雅5
1. 中国中医科学院医学实验中心, 北京 100700;
2. 内蒙古医科大学蒙医药学院, 内蒙古 呼和浩特 010110;
3. 内蒙古民族大学蒙医药学院, 内蒙古 通辽 028000;
4. 中央民族大学药学院, 北京 100081;
5. 中国中医科学院中医药研究发展中心, 北京 100700
摘要:
利用网络药理学的方法,建立诃子解草乌毒性的活性成分-作用靶点-通路的网络图,对作用靶点的基因功能和通路进行富集分析,探讨传统蒙医理论诃子解草乌心脏毒性的作用机制。通过TCMSP数据库、台湾中医药资料库获得诃子主要活性成分,采用SwissTargetPrediction预测活性成分的潜在靶点并于OMIM、TTD、DiGSeE三个疾病靶点数据进行比对,获得诃子解草乌心脏毒性的作用靶点。采用Metascape数据库平台对作用靶点的GO(Gene ontology)注释和KEGG通路进行富集分析和蛋白功能归属,并利用SystemsDock分子对接网站对诃子成分与靶点进行分子对接验证。最后通过Cytoscape构建诃子解草乌毒“活性成分-作用靶点-通路”网络图,最终发现诃子15个活性成分、40个作用靶点与其缓解草乌引起的心脏毒性相关。结果表明,诃子主要涉及配体受体结合、肌肉收缩、循环系统进程和细胞内外离子交换等生物过程并通过调节神经活性配体受体相互作用、钙离子信号通路、心肌细胞肾上腺素能信号等通路调节心脏功能进一步缓解草乌引起的心脏毒性。
关键词:    诃子      草乌毒性      蒙医理论      网络药理学      作用机制     
Mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity based on network pharmacology
LI Jian-liang1, LIANG Hui2, CAI Shu-zhen3, LI Zhi-yong4, TU Ya5
1. Medical Research Center, China Academy of Traditional Chinese Medicine, Beijing 100700, China;
2. Mongolian Medicine College, Inner Mongolia Medical University, Huhehaote 010110, China;
3. Mongolian Medicine College, Inner Mongolia University of Nationalities, Tongliao 028000, China;
4. Pharmacy College of Minzu University of China, Beijing 100081, China;
5. Development Research Center of TCM, China Academy of Traditional Chinese Medicine, Beijing 100700, China
Abstract:
The mechanism of detoxification of Chebulae Fructus against Aconiti kusnezoffii radix toxicity, which was known as Mongolian medical theory, was studied by establishing network of active components-targets-pathways of detoxification and enrichment analysis of targets and pathways based on network pharmacology. Firstly, the targets of active components collected from TCMSP and TCM Database@Taiwan were obtained through SwissTargetPrediction compared with disease targets from OMIM, TTD, DiGSeE. Then, the target enrichment analysis of GO functional annotations and KEGG pathways and protein function were analyzed by Metascape, furthermore, the action between main active ingredients and targets was assessed by SystemsDock Web Site. At last, the Cytoscape was used to construct the network of active components-targets-pathways. In conclusion, there were 15 components and 40 targets related to the cardiotoxicity caused by Aconiti kusnezoffii radix. Furthermore, Chebulae Fructus could regulate cardiac function to detoxify the toxicity by Aconiti kusnezoffii radix through the biological process of negative regulation of blood vessel diameter, regulation of ion transport circulatory system process, muscle contraction inorganic ion homeostasis and the pathways of neuroactive ligand-receptor interaction, calcium signaling pathway, adrenergic signaling in cardiomyocytes, etc.
Key words:    Chebulae Fructus    Aconiti kusnezoffii radix toxicity    Mongolian medical theory    network pharmacology    mechanism   
收稿日期: 2018-05-29
DOI: 10.16438/j.0513-4870.2018-0506
基金项目: 国家自然科学基金资助项目(81274192,81360677,81473797).
通讯作者: 图雅,Tel:86-10-64089691,E-mail:tuya126@126.com
Email: tuya126@126.com
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