基于网络药理学的四物汤治疗原发性痛经的作用机制研究
|
摘要
该文通过网络药理学研究预测四物汤治疗原发性痛经的多成分、多靶标、多途径作用机制,建立其"化合物-靶标-通路-疾病"的网络药理研究模式。利用网络药理学方法,针对已报道的四物汤活性成分,采用Swiss Target Prediction服务器依据反向药效团匹配方法预测四物汤活性成分靶标,并通过DrugBank,OMIM,TTD等数据库筛选出FDA批准的治疗原发性痛经靶标。通过对靶标的KEGG通路富集分析,采用Cytoscape软件构建四物汤"成分-靶标-通路-疾病"网络。网络分析表明,20个活性成分共涉及通路114条,预测出16个成分、16个靶标蛋白和24条通路与原发性痛经相关。四物汤可能通过作用于激素调节、中枢镇痛、解痉、炎症及免疫相关的蛋白靶标及通路,起到治疗原发性痛经的作用。该研究初步揭示了四物汤治疗原发性痛经的潜在活性成分及其可能的作用机制,为进一步的药效物质基础和作用机制实验研究提供了理论依据。
This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.
This paper aimed to predict and explore the mechanism of multiple components, targets and pathways of Siwu decoction for treatment of primary dysmenorrhea, and to establish a network pharmacological model of "compound-target-pathway-disease". According to the active ingredients in Siwu Decoction, Swiss Target Prediction server was used to predict the active component targets based on the reverse pharmacodynamic group matching method, and the primary dysmenorrhea targets approved by FDA were selected by database including DrugBank, OMIM and TTD. According to the enrichment analysis of the target pathways by using KEGG, the Cytoscape software was used to construct the network of "compound-target-pathway-disease" of Siwu Decoction. Network analysis showed that there were 20 active components involved in 114 pathways. And 16 components, 16 target proteins and 24 pathways were related to primary dysmenorrhea. Siwu Decoction may play a role in treating primary dysmenorrhea by acting on protein targets and pathways related to hormone regulation, central analgesia, spasmolysis,inflammation and immunity. This study revealed the potential active compounds and possible mechanism of Siwu Decoction for treatment of primary dysmenorrhea, providing theoretical references for further systematic laboratory experiments on effective compounds and action mechanism of Siwu Decoction.
引文
[1] 王艳英.原发性痛经发病机制及治疗的研究进展[J].中华中医药杂志,2015,30(7):2447.
[2] French L.Dysmenorrhea in adolescents:diagnosis and treatment[J].Pediatric Drugs,2008,10(1):1.
[3] Harada T,Momoeda M,Terakawa N,et al.Evaluation of a lowdose oral contraceptive pill for primary dysmenorrhea:a placebocontrolled,double-blind, randomized trial[J].Fertil Steril,2011,95(6):1928.
[4] 张丽君,李杰.妇产科病中医经验集成[M].武汉:湖北科学技术出版社,2012:107.
[5] 朱敏,段金廒,唐于平,等.四物汤及其组方药对与药味对小鼠原发性痛经模型的影响[J].中国实验方剂学杂志,2010,16(18):109.
[6] 吴红斌.桂枝四物汤配合熏蒸治疗原发性痛经临床观察[J].辽宁中医药大学学报,2009,11(8):141.
[7] 王巧英,赵兴国,李兆艾.香附四物汤对原发性痛经患者凝血功能的影响[J].中药材,2016,39(7):1670.
[8] 太平惠民和剂局.太平惠民和剂局方[M].陈庆平,陈冰鸥校注.北京:中国中医药出版社,1996:207.
[9] 周莉江,何瑶.四物汤对大鼠急性血瘀模型血液流变性作用的影响[J].中药药理与临床,2015,31(4):3.
[10] 刘婷婷,何瑶,王丽娟,等.HPLC同时测定四物汤中6种有效成分的含量[J].中药材,2016,39(7):1603.
[11] 何瑶,周莉江,刘婷婷,等.四物合剂提取纯化过程中不同中间产物补血调经作用研究[J].中药材,2016,39(3):646.
[12] 何瑶,王丽娟,刘婷婷,等.基于代谢组学技术分析四物汤治疗原发性痛经证的作用机制[J].中国实验方剂学杂志,2017,23(12):82.
[13] 柴程芝,余伯阳.从治疗原发性痛经新用途的发现探讨经方葛根汤现代研究的新思路[J].中国中药杂志,2018,43(12):2460.
[14] 吴纯伟,路丽,梁生旺,等.药物靶标预测技术在中药网络药理学中的应用[J].中国中药杂志,2016,41(3):377.
[15] Li Y,Zhang J,hang L,et al. Systems pharmacology to decipher the combinational antimigraine effects of Tianshu formula[J]. J Ethnopharmacol,2015,174(15): 45.
[16] Liu H,Wang J,Zhou W,et al. Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice[J]. J Ethnopharmacol,2013,146(3): 773.
[17] Xu X,Zhang W,Huang C,et al. A novel chemometric method for the prediction of human oral bioavailability[J]. Int J Mol Sci,2012,13 (6):6964.
[18] Ma C,Wang L,Xie X Q. GPU accelerated chemical similarity calculation for compound library comparison[J]. J Chem Inf Model,2011,51(7): 1521.
[19] Li J,Zhao P,Li Y,et al. Systems pharmacology based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease[J]. Sci Rep,2015,doi: 10.1038/srep15290.
[20] Cousins K R. Computer review of Chem Draw Ultra 12.0[J]. J Am Chem Soc,2011,133(21): 83.
[21] Liu X,Ouyang S,Yu B,et al. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach[J]. Nucl Acids Res,2010,doi:10.1093/nar/gkq300.
[22] 龙红萍,蔺晓源,王宇红,等.基于网络药理学研究复方钩藤降压片治疗高血压的作用机制 [J].中国中药杂志,2018,43(7):1360.
[23] Smoot M E,Ono K,Ruscheinski J,et al. Cytoscape 2.8: new features for data integration and network visualization[J].Bioinformatics,2011,27:431.
[24] Saito R,Smoot M E,Ono K,et al. A travel guide to Cytoscape plugins[J]. Nat Methods,2012,doi:10.1038/nmeth.2212.
[25] 李亚洲,佟继铭.原发性痛经发病机制与治疗[J].承德医学院学报,2011,28(2):193.
[26] 钱之玉.药理学[M]. 3版. 北京:中国医药科技出版社,2000:327.
[27] 赵敏珍,应延风.环氧化酶和痛经相关性研究进展[J].现代中西医结合杂志,2008,17(23):3712.
[28] 刘培,段金廒,白钢,等.用于妇科血瘀证原发性痛经的四物汤类方主要活性成分网络药理学分析[J].中国中药杂志,2014,39(1):113.
[29] Abu J I,Konje J C. Leukotrienes in gynaecology:the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis[J]. Hum Reprod Update,2000,6(2):200.
[30] 王小荣,邱明丰,谢国祥.当归油对痛经小鼠子宫组织中一氧化氮和钙离子的影响[J].时珍国医国药,2006,17(5):723.
[31] Brown R E,Stevens D R,Haas H L. The physiology of brain histamine[J].Prog Neurobio,2001,63(6):637.
[32] Dai N,Fang L,Li Y B,et al. Effect of jingqian zhitong fang on serum sex hormone levels in women with primary dysmenorrhea[J]. Evid Based Complement Alternat Med,2014,2014:876431.
[33] 李继俊.妇产科内分泌治疗学[M]. 北京: 人民军医出版社,2005:341.
[34] 成泽东,栗冬,陈以国.温和灸对原发性痛经大鼠T细胞亚群水平的影响[J].中华中医药学刊,2012,30(11):2458.
[2] French L.Dysmenorrhea in adolescents:diagnosis and treatment[J].Pediatric Drugs,2008,10(1):1.
[3] Harada T,Momoeda M,Terakawa N,et al.Evaluation of a lowdose oral contraceptive pill for primary dysmenorrhea:a placebocontrolled,double-blind, randomized trial[J].Fertil Steril,2011,95(6):1928.
[4] 张丽君,李杰.妇产科病中医经验集成[M].武汉:湖北科学技术出版社,2012:107.
[5] 朱敏,段金廒,唐于平,等.四物汤及其组方药对与药味对小鼠原发性痛经模型的影响[J].中国实验方剂学杂志,2010,16(18):109.
[6] 吴红斌.桂枝四物汤配合熏蒸治疗原发性痛经临床观察[J].辽宁中医药大学学报,2009,11(8):141.
[7] 王巧英,赵兴国,李兆艾.香附四物汤对原发性痛经患者凝血功能的影响[J].中药材,2016,39(7):1670.
[8] 太平惠民和剂局.太平惠民和剂局方[M].陈庆平,陈冰鸥校注.北京:中国中医药出版社,1996:207.
[9] 周莉江,何瑶.四物汤对大鼠急性血瘀模型血液流变性作用的影响[J].中药药理与临床,2015,31(4):3.
[10] 刘婷婷,何瑶,王丽娟,等.HPLC同时测定四物汤中6种有效成分的含量[J].中药材,2016,39(7):1603.
[11] 何瑶,周莉江,刘婷婷,等.四物合剂提取纯化过程中不同中间产物补血调经作用研究[J].中药材,2016,39(3):646.
[12] 何瑶,王丽娟,刘婷婷,等.基于代谢组学技术分析四物汤治疗原发性痛经证的作用机制[J].中国实验方剂学杂志,2017,23(12):82.
[13] 柴程芝,余伯阳.从治疗原发性痛经新用途的发现探讨经方葛根汤现代研究的新思路[J].中国中药杂志,2018,43(12):2460.
[14] 吴纯伟,路丽,梁生旺,等.药物靶标预测技术在中药网络药理学中的应用[J].中国中药杂志,2016,41(3):377.
[15] Li Y,Zhang J,hang L,et al. Systems pharmacology to decipher the combinational antimigraine effects of Tianshu formula[J]. J Ethnopharmacol,2015,174(15): 45.
[16] Liu H,Wang J,Zhou W,et al. Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice[J]. J Ethnopharmacol,2013,146(3): 773.
[17] Xu X,Zhang W,Huang C,et al. A novel chemometric method for the prediction of human oral bioavailability[J]. Int J Mol Sci,2012,13 (6):6964.
[18] Ma C,Wang L,Xie X Q. GPU accelerated chemical similarity calculation for compound library comparison[J]. J Chem Inf Model,2011,51(7): 1521.
[19] Li J,Zhao P,Li Y,et al. Systems pharmacology based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease[J]. Sci Rep,2015,doi: 10.1038/srep15290.
[20] Cousins K R. Computer review of Chem Draw Ultra 12.0[J]. J Am Chem Soc,2011,133(21): 83.
[21] Liu X,Ouyang S,Yu B,et al. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach[J]. Nucl Acids Res,2010,doi:10.1093/nar/gkq300.
[22] 龙红萍,蔺晓源,王宇红,等.基于网络药理学研究复方钩藤降压片治疗高血压的作用机制 [J].中国中药杂志,2018,43(7):1360.
[23] Smoot M E,Ono K,Ruscheinski J,et al. Cytoscape 2.8: new features for data integration and network visualization[J].Bioinformatics,2011,27:431.
[24] Saito R,Smoot M E,Ono K,et al. A travel guide to Cytoscape plugins[J]. Nat Methods,2012,doi:10.1038/nmeth.2212.
[25] 李亚洲,佟继铭.原发性痛经发病机制与治疗[J].承德医学院学报,2011,28(2):193.
[26] 钱之玉.药理学[M]. 3版. 北京:中国医药科技出版社,2000:327.
[27] 赵敏珍,应延风.环氧化酶和痛经相关性研究进展[J].现代中西医结合杂志,2008,17(23):3712.
[28] 刘培,段金廒,白钢,等.用于妇科血瘀证原发性痛经的四物汤类方主要活性成分网络药理学分析[J].中国中药杂志,2014,39(1):113.
[29] Abu J I,Konje J C. Leukotrienes in gynaecology:the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis[J]. Hum Reprod Update,2000,6(2):200.
[30] 王小荣,邱明丰,谢国祥.当归油对痛经小鼠子宫组织中一氧化氮和钙离子的影响[J].时珍国医国药,2006,17(5):723.
[31] Brown R E,Stevens D R,Haas H L. The physiology of brain histamine[J].Prog Neurobio,2001,63(6):637.
[32] Dai N,Fang L,Li Y B,et al. Effect of jingqian zhitong fang on serum sex hormone levels in women with primary dysmenorrhea[J]. Evid Based Complement Alternat Med,2014,2014:876431.
[33] 李继俊.妇产科内分泌治疗学[M]. 北京: 人民军医出版社,2005:341.
[34] 成泽东,栗冬,陈以国.温和灸对原发性痛经大鼠T细胞亚群水平的影响[J].中华中医药学刊,2012,30(11):2458.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |