Zou Chun-Cai, Yan Hai-Yan, Wang Li-Li, Bian Ying-Ying
Pharmacy School of Wannan Medical College Wuhu 241002,China.
Zhongguo Zhong Yao Za Zhi. 2019 Apr;44(8):1654-1659. doi: 10.19540/j.cnki.cjcmm.20190111.003.
To explore the anti-platelet aggregation and anti-thrombotic mechanisms of Trichosanthis Fructus combined with aspirin based on network pharmacology and the validation of arteriovenous by pass model in rats. The databases of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome(DRAR-CPI),Universal Protein Resource(Uniprot) and the Database for Annotation,Visualization,and Integrated Discovery(DAVID) were used to predict protein targets and analyze biological pathway and signal pathway in the combination of Trichosanthis Fructus with aspirin. The effects of pretreatment with Trichosanthis Fructus pellets,aspirin pellets and their combination on thromboxane B2(TXB2),6-keto prostaglandin F1α(6-keto-PGF1α) and cyclic adenosine monophosphate(c AMP) in rat thrombotic model were studied. Through the study of network pharmacology,12 components of aspirin and Trichosanthis Fructus,including hydroxygenkwanin,quercetin and adenosine,were found to show the anti-platelet aggregation and anti-thrombosis mechanisms through9 common protein targets,such as SRC,RAC1,MAPK14,MAPK1,AKT1,and 14 common signaling pathways,such as VEGF signaling pathway. After the intervention with Trichosanthis Fructus pellets combined with aspirin pellets,the vascular endothslia growth factor(VEGF) signaling pathway can be activated to inhibit platelet aggregation and improve vascular endothelial function,and show the anti-platelet aggregation and anti-thrombosis mechanisms,which verify the results of the network pharmacology,and explain the anti-platelet aggregation and anti-thrombotic mechanisms of the combination of Trichosanthis Fructus pellets with aspirin pellets.
基于网络药理学及大鼠动静脉旁路模型验证，探讨瓜蒌与阿司匹林联用的抗血小板聚集及抗血栓形成机制。运用中药系统药理学数据库与分析平台（TCMSP）、药物重定位与药物不良反应化学-蛋白质相互作用组（DRAR-CPI）、通用蛋白质资源（Uniprot）以及注释、可视化和集成发现数据库（DAVID）预测蛋白质靶点，分析瓜蒌与阿司匹林联用的生物途径和信号通路。研究瓜蒌丸、阿司匹林丸及其联用对大鼠血栓形成模型中血栓素B2（TXB2）、6-酮前列腺素F1α（6-keto-PGF1α）和环磷酸腺苷（cAMP）的影响。通过网络药理学研究发现，阿司匹林和瓜蒌的12种成分，包括羟基芫花素、槲皮素和腺苷等，通过9个共同的蛋白质靶点，如SRC、RAC1、MAPK14、MAPK1、AKT1等，以及14条共同的信号通路，如VEGF信号通路等发挥抗血小板聚集和抗血栓形成机制。瓜蒌丸与阿司匹林丸联用干预后可激活血管内皮生长因子（VEGF）信号通路，抑制血小板聚集，改善血管内皮功能，呈现抗血小板聚集和抗血栓形成机制，验证了网络药理学结果，阐释了瓜蒌丸与阿司匹林丸联用的抗血小板聚集和抗血栓形成机制。
