基于网络药理学的脑震宁颗粒治疗脑外伤的机制分析
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摘要
目的借助网络药理学技术预测脑震宁颗粒主要成分的潜在作用靶点,探讨其治疗脑外伤多成分-多靶点-多通路的作用机制。方法依据反向分子对接服务器(DRAR-CPI)和Coo LGe N数据库预测和筛选脑震宁颗粒主要成分的作用靶点;采用Cytoscape软件Clue GO插件对靶点进行GO富集分析,借助生物信息学注释数据库(DAVID)对获取的靶点信息进行KEGG通路注释分析;采用Cytoscape软件构建药材-成分-靶点-通路-疾病网络。结果脑震宁颗粒的33个主要成分涉及丝裂原活化蛋白激酶-1(MAPK1)、胱天蛋白酶-3(CASP3)、糖原合成酶激酶-3β(GSK3B)等34个靶点,GO富集分析和KEGG通路注释分析提示脑震宁颗粒可作用于活性氧的生物合成、平滑肌细胞增殖等生物过程,以及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、MAPK通路、JAK/STAT、m TOR等信号转导通路;网络分析显示脑震宁颗粒的作用机制可能与调控氧化应激、抑制炎症反应和神经细胞凋亡、调节脑内硫化氢生成和纤溶酶原(PLG)活性、改善认知功能及脑外伤后抑郁等相关。结论揭示了脑震宁颗粒多成分、多靶点、多通路的作用机制,为进一步深入研究脑震宁颗粒药效物质基础及作用机制奠定了基础。
Objective To predict the targets of the main ingredients in Naozhenning Granule and explore its molecular mechanism of multi-components, multi-targets, and multi-pathways. Methods Reverse molecular docking(DRAR-CPI) and Coo LGe N database were used to predict and screen the targets of Naozhenning Granule; GO enrichment was performed in Clue GO of Cytoscape; KEGG pathway analysis was conducted in DAVID database; The herbs-ingredients-targets-pathways-disease network was constructed in the Cytoscape software. Results A total of 33 candidate compounds were screened out, and a total of 34 potential targets were revealed for Naozhenning Granule, such as MAPK1, CASP3, and GSK3 B. The results of GO enrichment and KEGG pathway analysis indicated that Naozhenning Granule was involved in a series of biological process, such as reactive oxygen species biosynthetic process and positive regulation of smooth muscle cell proliferation as well as some signaling pathways, including PI3 K/Akt, MAPK, JAK/STAT, and m TOR. The herbs-ingredients-targets-pathways-disease network suggested that the mechanism of Naozhenning Granule was involved with the regulation of oxidative stress, inhibiting the inflammatory response and the apoptosis of neural cells, regulation of the formation of H_2S and the activity of PLG, improving the cognitive function and post traumatic depression. Conclusion The study suggested that the molecular mechanism of Naozhenning Granule was related with the multi-components, multi-targets, and multi-pathways, which provided a scientific basis for further elucidation of the active ingredients and pharmacological action of Naozhenning Granule.
Objective To predict the targets of the main ingredients in Naozhenning Granule and explore its molecular mechanism of multi-components, multi-targets, and multi-pathways. Methods Reverse molecular docking(DRAR-CPI) and Coo LGe N database were used to predict and screen the targets of Naozhenning Granule; GO enrichment was performed in Clue GO of Cytoscape; KEGG pathway analysis was conducted in DAVID database; The herbs-ingredients-targets-pathways-disease network was constructed in the Cytoscape software. Results A total of 33 candidate compounds were screened out, and a total of 34 potential targets were revealed for Naozhenning Granule, such as MAPK1, CASP3, and GSK3 B. The results of GO enrichment and KEGG pathway analysis indicated that Naozhenning Granule was involved in a series of biological process, such as reactive oxygen species biosynthetic process and positive regulation of smooth muscle cell proliferation as well as some signaling pathways, including PI3 K/Akt, MAPK, JAK/STAT, and m TOR. The herbs-ingredients-targets-pathways-disease network suggested that the mechanism of Naozhenning Granule was involved with the regulation of oxidative stress, inhibiting the inflammatory response and the apoptosis of neural cells, regulation of the formation of H_2S and the activity of PLG, improving the cognitive function and post traumatic depression. Conclusion The study suggested that the molecular mechanism of Naozhenning Granule was related with the multi-components, multi-targets, and multi-pathways, which provided a scientific basis for further elucidation of the active ingredients and pharmacological action of Naozhenning Granule.
引文
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[31]潘云,骆喜宝,陈燕.乌司他丁对脑缺血再灌注损伤大鼠血浆抗凝血酶III活性及纤溶酶原活性的影响[J].广东医学,2011,32(20):2640-2642.
[2]张明升,孙殿春,高尚进,等.脑震宁冲剂的药效学实验研究[J].中成药,1997,19(6):33-34.
[3]王学建,季炜鹏.脑震宁治疗脑外伤后头痛53例疗效观察[J].中华神经创伤外科电子杂志,2017,3(5):292-293.
[4]阮观忠.脑震宁治疗脑震荡后综合症102例[J].福建中医药,2000(3):51.
[5]王晓明.脑震宁冲剂对颅内血肿病人术后康复的作用[J].现代康复,2001,5(6):127.
[6]Liu C X,Liu R,Fan H R,et al.Network pharmacology bridges traditional application and modern development of traditional Chinese medicine[J].Chin Herb Med,2015,7(1):3-17.
[7]王昊,赵振宇,沈霞,等.基于系统药理学研究远志治疗阿尔茨海默病的作用机制[J].药学学报,2017,52(10):1554-1561.
[8]董亚楠,韩彦琪,王磊,等.基于网络药理学的六经头痛片治疗偏头痛的作用机制探讨[J].中草药,2017,48(20):4174-4180.
[9]袁荣高,顾明华,古江勇.基于网络药理学研究大川芎方治疗偏头痛的作用机制[J].南京中医药大学学报,2016,32(6):571-576.
[10]张潇,高耀,向欢,等.基于网络药理学的交泰丸治疗抑郁症作用机制研究[J].中草药,2017,48(8):1584-1590.
[11]黄慧玲,刘锐,王琴,等.亚低温对颅脑创伤大鼠脑线粒体活性氧和ATP酶合成能力的影响[J].天津医药,2008,36(6):438-440.
[12]王建宇,王伯良,田小溪,等.神经节苷脂联合高压氧对重度脑外伤急性期患者凝血功能的影响及促醒作用[J].现代生物医学进展,2017,17(9):1674-1677.
[13]郁迪,莫绪明.PI3K/Akt和MAPK信号通路在缺血性脑损伤中的保护作用[J].医学综述,2015,21(2):210-213.
[14]薛翔,刘红梅,邵旦兵,等.JAK/STAT信号通路调节机制的研究进展[J].现代生物医学进展,2015,15(11):2161-2165.
[15]崔小芬,李鑫鑫,张丽丽,等.小胶质细胞介导的炎性反应在缺血再灌注引起脑损伤中的作用研究进展[J].世界最新医学信息文摘,2017,17(86):83-85.
[16]徐祥.m TOR信号通路在蛛网膜下腔出血后早期脑损伤中的作用及机制研究[D].苏州:苏州大学,2015.
[17]王刚,董晓巧,杜权,等.氧化苦参碱抗大鼠脑外伤后神经细胞凋亡及机制研究[J].中国现代应用药学,2012,29(4):289-294.
[18]Kunz A,Dirnagl U,Mergenthaler P.Acute pathophysiological processes after ischaemic and traumatic brain injury[J].Best Pract Res ClinAnaesthesiol,2010,24(4):495-509.
[19]袁静.虫草素改善脑外伤大鼠模型中血脑屏障损害的机制研究[D].济南:山东大学,2017.
[20]Das M,Leonardo C C,Rangooni S,et al.Lateral fluid percussion injury of the brain induces CCL20inflammatory chemokine expression in rats[J].JNeuroinflammation,2011,8(2):148-148.
[21]施宏.丙酮酸乙酯对脑外伤后大鼠的神经保护作用及其机制研究[D].上海:复旦大学,2012.
[22]马允,杨帆,昂文平.针刺对脑损伤保护机制的实验研究进展[J].广州中医药大学学报,2013,30(1):120-124.
[23]刘海婷,母得志.诱导型一氧化氮合酶和缺氧缺血脑损伤[J].中国当代儿科杂志,2014,16(9):962-967.
[24]董勇.通窍活血汤加味结合西药治疗脑外伤认知障碍的疗效观察[D].沈阳:辽宁中医药大学,2015.
[25]宋祯彦,王珊珊,贺旭,等.网络药理学方法研究石菖蒲治疗神经退行性疾病的作用机制[J].湖南中医药大学学报,2017,37(8):848-855.
[26]孙楷,孙凡,朱亮.单胺氧化酶抑制剂在临床方面的应用[J].现代生物医学进展,2014,14(6):1180-1182.
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[28]谢惠芳,徐如祥,魏继鹏,等.JAK2/STAT3信号转导通路在缺血性脑损伤中作用机制的研究[J].中风与神经疾病杂志,2008,25(2):135-138.
[29]刘林玉,杜司晨,张进,等.戈谢氏病致病机制及治疗方法[J].遗传,2015,37(6):510-516.
[30]邵建林,朱俊超,吴滨阳,等.异氟醚、七氟醚和地氟醚预处理对脑缺血再灌注损伤大鼠海马CBS/H_2S、i NOS/NO和HO-1/CO的影响[J].中华麻醉学杂志,2006,26(10):907-910.
[31]潘云,骆喜宝,陈燕.乌司他丁对脑缺血再灌注损伤大鼠血浆抗凝血酶III活性及纤溶酶原活性的影响[J].广东医学,2011,32(20):2640-2642.