Synergistic Effects of Chuanxiong-Chishao Herb-Pair on Promoting Angiogenesis at Network Pharmacological and Pharmacodynamic Levels  

作　　者：WANG Yan GUO Gang YANG Bin-rui XIN Qi-qi LIAO Qi-wen LEE Simon Ming-Yuen HU Yuan-jia CHEN Ke-ji CONG Wei-hong 

机构地区：[1]Clinical Medical College, Beijing University of Chinese Medicine [2]Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences [3]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macao [4]Department of Acupuncture and Moxibustion, Qilu Hospital Affiliated to Shandong University

出　　处：《Chinese Journal of Integrative Medicine》2017年第9期654-662,共9页中国结合医学杂志（英文版）

基　　金：Supported by Beijing Municipal Science and Technology Commission(No.Z141100002214011);the Science and Technology Development Fund of Macao SAR(No.069/2015/A2 and 134/2014/A3);Research Committee of University of Macao(No.MYRG2015-00182-ICMS-QRCM,MYRG2015-00214-ICMS-QRCM,MYRG139(Y1-L4)-ICMS12-LMY,and MYRG2016-00129-ICMS-QRCM),China

摘　　要：Objective： To investigate the synergistic effects of Chuanxiong-Chishao herb-pair （CCHP） on promoting angiogenesis in silico and in vivo. Methods： The mechanisms of action of an herb-pair, Chuanxiong- Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insufficiency model of transgenic zebrafish in vivo. The mRNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction （RT-PCR）. Results： The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflammatory effect and analgesics. Particularly, estrogen receptor α （ESR α） and hypoxia-inducible factor 1-α （HIF-1 α） were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride （TMpoHCI） and paeoniflorin （PF） promoted the regeneration of new blood vessels in zebrafish involving up-regulating ESR α mRNA expression. Co-treatment of TMP·HCI and PF could enhance the vessel sprouting in chemical-induced vascular insufficiency zebrafish at the optimal compatibility proportion of PF 10 μ mol/L with TMP·HCI 1 μ mol/L. Conclusions： The network pharmObjective： To investigate the synergistic effects of Chuanxiong-Chishao herb-pair （CCHP） on promoting angiogenesis in silico and in vivo. Methods： The mechanisms of action of an herb-pair, Chuanxiong- Chishao, were investigated using the network pharmacological and pharmacodynamic strategies involving computational drug target prediction and network analysis, and experimental validation. A set of network pharmacology methods were created to study the herbs in the context of targets and diseases networks, including prediction of target profiles and pharmacological actions of main active compounds in Chuanxiong and Chishao. Furthermore, the therapeutic effects and putative molecular mechanisms of Chuanxiong-Chishao actions were experimentally validated in a chemical-induced vascular insufficiency model of transgenic zebrafish in vivo. The mRNA expression of the predicted targets were further analyzed by real-time polymerase chain reaction （RT-PCR）. Results： The computational prediction results found that the compounds in Chuanxiong have antithrombotic, antihypertensive, antiarrhythmic, and antiatherosclerotic activities, which were closely related to protecting against hypoxic-ischemic encephalopathy, ischemic stroke, myocardial infarction and heart failure. In addition, compounds in Chishao were found to participate in anti-inflammatory effect and analgesics. Particularly, estrogen receptor α （ESR α） and hypoxia-inducible factor 1-α （HIF-1 α） were the most important potential protein targets in the predicted results. In vivo experimental validation showed that post-treatment of tetramethylpyrazine hydrochloride （TMpoHCI） and paeoniflorin （PF） promoted the regeneration of new blood vessels in zebrafish involving up-regulating ESR α mRNA expression. Co-treatment of TMP·HCI and PF could enhance the vessel sprouting in chemical-induced vascular insufficiency zebrafish at the optimal compatibility proportion of PF 10 μ mol/L with TMP·HCI 1 μ mol/L. Conclusions： The network pharm

关 键 词：TETRAMETHYLPYRAZINE paeoniflorin angiogenesis network pharmacology 

分 类 号：R285[医药卫生—中药学]