散结镇痛胶囊入血成分治疗子宫内膜异位症、子宫腺肌症及继发性痛经的作用机制探讨
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摘要
目的:分析散结镇痛胶囊治疗子宫内膜异位症、子宫腺肌症及继发性痛经的活性成分群和分子作用机制。方法:将散结镇痛胶囊的入血成分与子宫内膜异位症、子宫腺肌症及继发性痛经相关的靶点进行分子对接,选取对接得分较高的分子与靶蛋白构建药物-靶点网络图,分析网络特征。结果:网络分析结果表明散结镇痛胶囊中的6个成分可与子宫内膜异位症、子宫腺肌症及继发性痛经的87个靶点有较强的相互作用,进一步的分析阐明了散结镇痛胶囊的5个主要活性成分及23个潜在作用靶点。结论:散结镇痛胶囊的主要活性成分通过作用于炎症反应、细胞侵袭、凝血系统、平滑肌收缩、神经激素调节等靶点,来抑制子宫内膜的血管形成和血液循环、子宫平滑肌收缩、免疫炎症反应以及雌激素分泌,达到治疗子宫内膜异位症、子宫腺肌症及继发性痛经等病证的目的。
Objective:To analyze the pharmacological basis and molecular mechanism of Sanjie Zhentong capsule in the treatment of endometriosis,adenomyosis,secondary dysmenorrhea.Method:The 6 compounds of Sanjie Zhentong capsule showed stronger interactions with 87 proteins relating to endometriosis,adenomyosis,and secondary dysmenorrhea in molecular docking.Then the drug-target network was selected,and the network features were analyzed.Result:The molecular docking and network characteristics revealed 5 main active molecules and 23 potential targets of Sanjie Zhentong capsule.Conclusion:The main active ingredients of Sanjie Zhentong capsule have a trong inhibition effect on endometrial angiogenesis and blood circulation,uterine smooth muscle contraction,immune inflammatory reaction and estrogen secretion by acting on the targets of inflammation,cell invasion,metastasis,coagulation system,smooth muscle contraction and neurohormone regulation,so as to treat endometriosis,adenomyosis and secondary dysmenorrhea.
Objective:To analyze the pharmacological basis and molecular mechanism of Sanjie Zhentong capsule in the treatment of endometriosis,adenomyosis,secondary dysmenorrhea.Method:The 6 compounds of Sanjie Zhentong capsule showed stronger interactions with 87 proteins relating to endometriosis,adenomyosis,and secondary dysmenorrhea in molecular docking.Then the drug-target network was selected,and the network features were analyzed.Result:The molecular docking and network characteristics revealed 5 main active molecules and 23 potential targets of Sanjie Zhentong capsule.Conclusion:The main active ingredients of Sanjie Zhentong capsule have a trong inhibition effect on endometrial angiogenesis and blood circulation,uterine smooth muscle contraction,immune inflammatory reaction and estrogen secretion by acting on the targets of inflammation,cell invasion,metastasis,coagulation system,smooth muscle contraction and neurohormone regulation,so as to treat endometriosis,adenomyosis and secondary dysmenorrhea.
引文
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[22]张明发,沈雅琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459-461.
[23]徐仿周,陈昶,周学琴,等.浙贝乙素的镇痛活性及身体依赖性的实验研究[J].今日药学,2008,18(6):4-6.
[24]XU J,ZHAO W,PAN L,et al.Peimine,a main active ingredient of Fritillaria,exhibits anti-inflammatory and pain suppression properties at the cellular level[J].Fitoterapia,2016,111:1-6.
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[26]程雯,陈励藻,俞超芹.MAPK信号通路与子宫内膜异位症[J].生命的化学,2011,31(6):882-886.
[27]徐丛剑,程明军,黄宇婷,等.子宫内膜异位症病因学研究进展[J].中国实用妇科与产科杂志,2009,25(9):712-714.
[28]王晨泉.磷酸二酯酶与疾病相关的药理学研究进展[J].医学综述,2011,17(18):2806-2808.
[29]血管内皮生长因子及其受体在子宫内膜异位症中的表达和意义[J].中国免疫学杂志,2013,29(6):605-609.
[30]张爱群,孙富国,曾博文,等.MMP-13在卵巢子宫内膜异位症中的表达及临床意义[J].中国现代医学杂志,2011,21(1):61-63.
[31]袁国平,陈俊杰,谢芳.MMP-2、MMP-9及其组织抑制因子在子宫内膜异位症中的表达[J].中国卫生检验杂志,2014,24(9):1267-1268.
[32]孙淼,李妍,侯丽辉,等.子宫内膜异位症与雌激素合成相关酶的研究[J].现代妇产科进展,2011,20(5):401-402.
[2]SHAO L,FAN T P,WEI J,et al.Network pharmacology in traditional Chinese medicine[J].Evid-Based Compl Alt Ecam,2014,2014(1):138460.
[3]LI S,ZHANG B.Traditional Chinese medicine network pharmacology:theory,methodology and application[J].Chin J Nat Med,2013,11(2):110.
[4]张润桐,吴海宁,于桂红,等.基于网络药理学的淫羊藿防治疾病的优效组分及信号通路研究[J].中国中药杂志,2018,43(23):4709-4717.
[5]张立虎,李冬冬,萧伟,等.基于网络药理学与分子对接法预测银杏叶提取物的抗炎机制[J].中国实验方剂学杂志,2018,24(7):192-198.
[6]蒋海霞.MT1-MMP与RECK蛋白在子宫腺肌病中的表达及其与血管生成的关系[D].泸州:泸州医学院,2013.
[7]卢文丹,李莉,申艳佳,等.基于血管舒缩相关GPCR靶点的小续命汤网络药理学研究[J].中国中药杂志,2018,43(23):4698-4708.
[8]秦建平,吴建雄,李家春,等.散结镇痛胶囊中酚酸类成分的指纹图谱研究和多指标成分定量测定[J].中草药,2014,45(1):59-63.
[9]钱华.散结镇痛胶囊治疗100例子宫内膜异位症的疗效及跟踪调查[J].临床医药文献电子杂志,2017,4(52):10177-10178.
[10]沙余丽.用散结镇痛胶囊治疗子宫内膜异位症的效果观察[J].当代医药论丛,2016,15(15):90-91.
[11]曹芸.散结镇痛胶囊对子宫内膜异位症及子宫腺肌病痛经治疗效果观察[J].首都食品与医药,2017,24(12):79-80.
[12]彭秋菊,钟娘英.散结镇痛胶囊治疗子宫腺肌症痛经疗效观察[J].实用中医药杂志,2016,32(6):604-605.
[13]颜月园,萧伟,吴云,等.散结镇痛胶囊中皂苷类成分的指纹图谱研究[J].中草药,2012,43(3):496-500.
[14]颜月园.散结镇痛胶囊化学组分及入血成分研究[D]:南京:南京中医药大学,2012.
[15]柯志鹏,张新庄,丁玥,等.利用网络药理学方法研究芪桂痛风片的药效物质基础与分子作用机制[J].中国中药杂志,2015,40(14):2837-2842.
[16]张新庄,萧伟,徐筱杰,等.基于网络药理学的桂枝茯苓胶囊治疗痛经、子宫肌瘤和盆腔炎的分子作用机制研究[J].中草药,2016,47(1):81-94.
[17]GU J,GUI Y,CHEN L,et al.Use of natural products as chemical library for drug discovery and network pharmacology[J].PLo S One,2013,8(4):e62839.
[18]JIANG X,Kumar K,XIN H,et al.DOVIS 2.0:an efficient and easy to use parallel virtual screening tool based on Auto Dock 4.0[J].Chem Cent J,2008,2(1):1-7.
[19]张新庄,萧伟,徐筱杰,等.利用网络药理学方法研究热毒宁注射液抗流感病毒的分子作用机制[J].物理化学学报,2013,29(7):1415-1420.
[20]Smoot M E,Ono K,Ruscheinski J,et al.Cytoscape 2.8:new features for data integration and network visualization[J].Bioinformatics,2011,27(3):431-432.
[21]ZHANG X,GU J,CAO L,et al.Network pharmacology study on the mechanism of traditional Chinese medicine for upper respiratory tract infection[J].Mol Biosyst,2014,10(10):2517-2525.
[22]张明发,沈雅琴.浙贝母药理研究进展[J].上海医药,2007,28(10):459-461.
[23]徐仿周,陈昶,周学琴,等.浙贝乙素的镇痛活性及身体依赖性的实验研究[J].今日药学,2008,18(6):4-6.
[24]XU J,ZHAO W,PAN L,et al.Peimine,a main active ingredient of Fritillaria,exhibits anti-inflammatory and pain suppression properties at the cellular level[J].Fitoterapia,2016,111:1-6.
[25]YI P F,WU Y C,DONG H B,et al.Peimine impairs proinflammatory cytokine secretion through the inhibition of the activation of NF-κB and MAPK in LPS-induced RAW264.7 macrophages[J].Immunopharm Immunot,2013,doi:10.3109/08923973.2013.822508.
[26]程雯,陈励藻,俞超芹.MAPK信号通路与子宫内膜异位症[J].生命的化学,2011,31(6):882-886.
[27]徐丛剑,程明军,黄宇婷,等.子宫内膜异位症病因学研究进展[J].中国实用妇科与产科杂志,2009,25(9):712-714.
[28]王晨泉.磷酸二酯酶与疾病相关的药理学研究进展[J].医学综述,2011,17(18):2806-2808.
[29]血管内皮生长因子及其受体在子宫内膜异位症中的表达和意义[J].中国免疫学杂志,2013,29(6):605-609.
[30]张爱群,孙富国,曾博文,等.MMP-13在卵巢子宫内膜异位症中的表达及临床意义[J].中国现代医学杂志,2011,21(1):61-63.
[31]袁国平,陈俊杰,谢芳.MMP-2、MMP-9及其组织抑制因子在子宫内膜异位症中的表达[J].中国卫生检验杂志,2014,24(9):1267-1268.
[32]孙淼,李妍,侯丽辉,等.子宫内膜异位症与雌激素合成相关酶的研究[J].现代妇产科进展,2011,20(5):401-402.