基于网络药理学的豨莶通栓胶囊作用机制解析及抗炎作用研究
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摘要
豨莶通栓胶囊活血祛瘀、祛风化痰、舒筋活络、醒脑开窍,对中风病主症、中风病积分等有较好的疗效。该研究通过数据库检索获得豨莶通栓胶囊中药化学成分908个,基于反向找靶技术获得豨莶通栓胶囊潜在作用靶点337个,并利用其蛋白质相互作用信息构建豨莶通栓胶囊蛋白互作网络,对网络进行模块分析及模块功能注释。结果显示,豨莶通栓胶囊通过对体内脂质代谢、血压系统的调节作用对脑卒中发病的最直接的危险因素高血脂、高血压发挥治疗作用;通过对血液循环系统及神经系统的调节作用治疗脑卒中引发的脑血管血栓及脑组织供血、供氧不足引起神经组织的不可逆性死亡;并通过对炎症免疫反应的调节作用治疗脑卒中导致的体内炎症及伴随着炎症发展而产生的免疫学反应。基于网络分析结果,采用脂多糖(LPS)刺激RAW264. 7细胞构建体外细胞炎症反应模型,以Griess法检测NO的含量,探讨豨莶通栓胶囊抗炎作用,结果显示豨莶通栓胶囊可抑制炎症细胞对NO的释放能力,具有抗炎作用。该研究通过对豨莶通栓胶囊功能模块的分析,并通过部分实验验证,以期从分子网络水平上探讨豨莶通栓胶囊的作用机制,为其临床应用提供科学依据。
Xixian Tongshuan Capsules with functions of promoting blood circulation and removing blood stasis,dispelling wind and resolving phlegm,relaxing muscles and activating collaterals,restoring consciousness and inducing resuscitation,has significant effects on main and concurrently symptoms of apoplexy. In this research,908 chemical compounds of Xixian Tongshuan Capsules were collected,and 337 potential targets were discovered by pharmacophore based reverse target identification. Protein interaction network( PIN)was then constructed and Identifying Protein Complex Algorithm( IPCA) was used to obtain the modules of the capsule and analyze the potential action mechanism. According to the research,Xixian Tongshuan Capsules could play a therapeutic role for hyperlipidemia and hypertension by regulating lipid metabolic process and blood pressure,the most direct risk factors of apoplexy. It could be used to treat the cerebral thrombosis and irreversible death of nerve tissue caused by insufficient supply of cerebral tissue blood and oxygen,in a way of regulating blood circulation system and nervous system. Xixian Tongshuan Capsules could also treat stroke-induced inflammation and inflammatory immune response through its regulatory effect on inflammatory immune response. Based on the network analysis,the antiinflammatory activity of Xixian Tongshuan Capsules extracts was investigated by measuring the NO release with Griess reagent method through LPS-induced in vitro inflammation model of RAW264. 7 cells. The results showed that Xixian Tongshuan Capsules extracts inhibited the secretion of NO by LPS-induced RAW264. 7 cells,indicating favorable anti-inflammatory activity. This research illuminates the mechanism of Xixian Tongshuan Capsules based on the PIN analysis at molecular network level,providing a scientific basis for its clinical application.
Xixian Tongshuan Capsules with functions of promoting blood circulation and removing blood stasis,dispelling wind and resolving phlegm,relaxing muscles and activating collaterals,restoring consciousness and inducing resuscitation,has significant effects on main and concurrently symptoms of apoplexy. In this research,908 chemical compounds of Xixian Tongshuan Capsules were collected,and 337 potential targets were discovered by pharmacophore based reverse target identification. Protein interaction network( PIN)was then constructed and Identifying Protein Complex Algorithm( IPCA) was used to obtain the modules of the capsule and analyze the potential action mechanism. According to the research,Xixian Tongshuan Capsules could play a therapeutic role for hyperlipidemia and hypertension by regulating lipid metabolic process and blood pressure,the most direct risk factors of apoplexy. It could be used to treat the cerebral thrombosis and irreversible death of nerve tissue caused by insufficient supply of cerebral tissue blood and oxygen,in a way of regulating blood circulation system and nervous system. Xixian Tongshuan Capsules could also treat stroke-induced inflammation and inflammatory immune response through its regulatory effect on inflammatory immune response. Based on the network analysis,the antiinflammatory activity of Xixian Tongshuan Capsules extracts was investigated by measuring the NO release with Griess reagent method through LPS-induced in vitro inflammation model of RAW264. 7 cells. The results showed that Xixian Tongshuan Capsules extracts inhibited the secretion of NO by LPS-induced RAW264. 7 cells,indicating favorable anti-inflammatory activity. This research illuminates the mechanism of Xixian Tongshuan Capsules based on the PIN analysis at molecular network level,providing a scientific basis for its clinical application.
引文
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[27]马津真,赵文慧,聂晓静,等.不同方法提取的铁皮石斛提取物对自发性高血压大鼠的降压作用及其机制研究[J].中国现代应用药学,2018,35(12):1811.
[2]滕天立,徐世芳,陈峰阳,等.中药豨莶草的化学成分及其药理作用研究进展[J].中国现代应用药学,2015,32(2):250.
[3]陈艳昆,乔连生,霍晓乾,等.基于计算机辅助水解和蛋白互作网络的珍珠母寡肽作用机制解析[J].中国中药杂志,2017,42(17):3417.
[4]Li M,Li D,Tang Y,et al. CytoCluster:a cytoscape plugin for cluster analysis and visualization of biological networks[J]. Int J Mol Sci,2017,18(9):1880.
[5]李倩,伍雪英.脑卒中高危因素探讨与分析[J].现代预防医学,2014,41(17):3262.
[6]高强,何成奇.脑梗死生化指标及其临床意义的国内研究进展[J].中国康复医学杂志,2009,24(2):190.
[7]唐朝克,杨永宗. LXR和ABCA1对体内胆固醇代谢的调节作用[J].生命的化学,2003,23(5):381.
[8]陶妍,吴高峰,杨建成,等. PPAR-α在酒精性脂肪肝发生中的作用研究进展[J].动物医学进展,2012,33(2):71.
[9]Davidson M H. Squalene synthase inhibition:a novel target for the management of dyslipidemia[J]. Curr Atheroscler Rep,2007,9(1):78.
[10]孙奎亮,杨凡喜,王军,等.脑卒中的炎症免疫机制研究进展[J].中国老年学杂志,2015,35(18):5360.
[11]魏伟.炎症免疫反应软调节[J].中国药理学通报,2016,32(3):297.
[12]陈妍,蒋宇扬. T淋巴细胞抗乳腺癌分子机制的研究[C].济南:全国免疫学学术大会,2014.
[13]谢周令,张俊朋,胡珀,等.脾酪氨酸激酶抑制剂的研究进展[J].中国新药杂志,2014(5):557.
[14]李永旺,王保国. Toll样受体信号转导通路介导的脑缺血耐受[J].中国药理学通报,2006,22(1):9.
[15]陈钊,张亚鲁,马阳,等.小分子IRAK-4抑制剂的研究进展[J].中南药学,2015(10):1017.
[16]何新华,郑志兵,李松.酪氨酸激酶Jak3抑制剂的研究进展[J].中国药物化学杂志,2005,15(6):373.
[17]王澳轩,刘冰妮,刘颖,等.抑制JAK3激酶的免疫抑制剂托法替尼[J].药物评价研究,2014,37(2):169.
[18]宋玉民,王莉,姚小强.具抗凝血作用的三种钕配合物与人血清白蛋白的相互作用[J].无机化学学报,2013,29(1):81.
[19]邢峻豪,杨凌云,李清,等.抗血栓药物的研究进展[J].药学进展,2014(3):174.
[20]Lwenberg E C,Meijers J C,Monia B P,et al. Coagulation factor XI as a novel target for antithrombotic treatment[J].J Thromb Haemost,2010,8(11):2349.
[21]许荔新,李凤才,师海波,等.豨莶通栓胶囊药效学研究[J].中草药,1999(3):208.
[22]马晓燕. c-Abl抑制剂应用于治疗帕金森病的进展研究[J].医学研究生学报,2017,30(6):653.
[23]Schlatterer S D,Acker C M,Davies P. c-Abl in neurodegenerative disease[J]. J Mol Neurosci,2011,45(3):445.
[24]卞雷斯. Trk受体在脑缺血中表达以及激活特性的研究[D].上海:上海交通大学,2010.
[25]潘明罗,邵大荣,刘燕红,等.缺血脑卒中和出血脑卒中危险因素的比较研究[J].中华疾病控制杂志,2015,19(9):883.
[26]陶蓉.肾素-血管紧张素系统抑制剂治疗高血压的研究进展[J].上海医药,2013(19):10.
[27]马津真,赵文慧,聂晓静,等.不同方法提取的铁皮石斛提取物对自发性高血压大鼠的降压作用及其机制研究[J].中国现代应用药学,2018,35(12):1811.