大黄黄连泻心汤有效成分的药理作用机制研究
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摘要
目的:基于网络药理明确大黄黄连泻心汤有效成分发挥药理作用的分子机制。方法:基于TCSMP平台,参照相关参数:OB≥50%,DL≥0.18,MW-2≤ALog P≤5,MW≤500,筛选大黄、黄连有效化学成分,构建大黄黄连泻心汤化学成分-靶点网络模型。基于CTD、TCMSP、DrugBank和UniProt筛选大黄、黄连有效化学成分的靶点,靶标通过数据库相互验证。通过DAVID 6.8对靶标进行通路富集、分子功能分析。靶标相互作用分析基于STRING。结果:大黄黄连泻心汤有效化学成分7个,黄连5个有效化学成分筛选出19个靶点,涉及12条通路。大黄27个靶点,涉及23条通路。NOS2为黄连、大黄共有靶点。相互作用分析发现黄连以VEGFA、IL-8、CCL2和AHR等靶标为中心节点。大黄主要以TP53、TNF、PTGS2、PIK3CG、MYC和CASP3等靶标为中心节点。结论:大黄黄连泻心汤有效成分的靶标在疾病中发挥作用具有协同作用。
Objective: Pharmacological molecular mechanism of the effective ingredients of Dahuang(rheum officinale) and Huanglian(coptis chinensis) based on network pharmacology. Methods: OB ≥50%, DL ≥0.18,MW-2≤ALog P≤5 and MW≤500 retrieval of effective chemical composition of Dahuang Huanglian Xiexin decoction based on TCMSP. Establishment of component and target of Dahuang Huanglian Xiexin decoction. Retrieval of potential therapeutic targets of Dahuang(rheum officinale) and Huanglian(coptis chinensis) based on CTD, TCMSP, DrugBank, UniProt. Target by mutual authentication of database. The potential targets were pathway analysis and molecular function analyzed by DAVID6.8, gene interaction by STRING. Results: Atotal of 7 effective chemical composition of Dahuang Huanglian Xiexin decoction. Collection of 19 corresponding targets and 12 pathways of Huanglian(coptis chinensis). collection of 27 corresponding targets and 23 pathways of Dahuang(rheum officinale). NOS2 is a common target. The central node of is the target of Huanglian(coptis chinensis) VEGFA, IL-8, CCL2, AHR and so on. The central node of is the target of Dahuang(rheum officinale)TP53, TNF, PTGS2, PIK3 CG, MYC and CASP3. Conclusion: Clear and effective ingredients of Dahuang Huanglian Xiexin decoction in the target disease play a role in synergistic action. Objective to provide theoretical guidance for target genes selection of Dahuang Huanglian Xiexin decoction.
Objective: Pharmacological molecular mechanism of the effective ingredients of Dahuang(rheum officinale) and Huanglian(coptis chinensis) based on network pharmacology. Methods: OB ≥50%, DL ≥0.18,MW-2≤ALog P≤5 and MW≤500 retrieval of effective chemical composition of Dahuang Huanglian Xiexin decoction based on TCMSP. Establishment of component and target of Dahuang Huanglian Xiexin decoction. Retrieval of potential therapeutic targets of Dahuang(rheum officinale) and Huanglian(coptis chinensis) based on CTD, TCMSP, DrugBank, UniProt. Target by mutual authentication of database. The potential targets were pathway analysis and molecular function analyzed by DAVID6.8, gene interaction by STRING. Results: Atotal of 7 effective chemical composition of Dahuang Huanglian Xiexin decoction. Collection of 19 corresponding targets and 12 pathways of Huanglian(coptis chinensis). collection of 27 corresponding targets and 23 pathways of Dahuang(rheum officinale). NOS2 is a common target. The central node of is the target of Huanglian(coptis chinensis) VEGFA, IL-8, CCL2, AHR and so on. The central node of is the target of Dahuang(rheum officinale)TP53, TNF, PTGS2, PIK3 CG, MYC and CASP3. Conclusion: Clear and effective ingredients of Dahuang Huanglian Xiexin decoction in the target disease play a role in synergistic action. Objective to provide theoretical guidance for target genes selection of Dahuang Huanglian Xiexin decoction.
引文
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[11] Zha Y,Gan P,Liu Q,et al.TP53 codon 72 polymorphism predicts efficacy of paclitaxel plus capecitabine chemotherapy in advanced gastric cancer patients[J].Arch Med Res,2016,47(1):13-18.
[12] Sarkar C,Ralte A M,Sharma M C,et al. Recurrent astrocytic tumours-a study of TP53 immunoreactivity and malignant progression[J]. Br J Neurosurg,2002,16(4):335-342.
[13]查纪坤,舒红兵.肿瘤坏死因子信号传导的分子机理[J].中国科学c(辑),2002,32(1):1-6.
[14] Tanaka Y,Martin Mola E. IL-6 targeting compared to TNF targeting in rheumatoid arthritis:studies of olokizumab,sarilumab and sirukumab[J].Ann Rheum Dis,2014,73(9):1595-1597.
[15]陈颖,张玉芳,李奕,等.Ptgds2基因在BXD重组近交系小鼠海马组织中的遗传基因组学分析[J].江苏医药,2011,37(20):2363-2365.
[16] Riedl S J, Shi Y. Molecular mechanisms of caspase regulation during apoptosis[J].Nat Rev Mol Cell Biol,2004,5(11):897-907.
[2]杨行堂,王志荣,王芝珺.黄连素对幽门螺杆菌抗菌作用的实验研究[J].同济大学学报(医学版),2014,35(6):63-66.
[3]徐萍,顾治平.黄连的药理作用研究进展[J].临床医药文献杂志,2017,4(27):5333-5336.
[4]李锋,王胜春,王新,等.大黄泻下效应的药理学新解释[J].中国中药杂志,2008,33(4):481-484.
[5]宫庆东,张沁园,王洪海.大黄黄连泻心汤历史源流及古今应用[J].山东中医药大学学报,2014,38(1):5-7.
[6]张文娟,王永华.系统药理学原理、方法及在中医药中的应用[J].世界中医药,2015,10(2):280-286.
[7]朱松莹,魏长良,吕晓霞.诱生型一氧化氮合酶在肺癌组织中的表达及其意义[J].徐州医学院学报,2001,21(4):285-288.
[8] Yu S,Sun J,Zhang J,e t al. Aberrant expression and association of VEGF and Dll4/Notch pathway molecules under hypoxia in patients with lung cancer[J]. Histol Histopathol,2013,28(2):277-284.
[9]余建明,刘喜德,曲丕盛,等.祛痹镇痛方对胶原诱导性关节炎大鼠滑膜IL-1β、IL-8、VEGF表达的影响[J].中国中西医结合杂志,2013,33(1):105-109.
[10]姜懿纳,陈乃宏.CCL2/MCP1在其相关疾病的机制研究[J].中国药理学通报,2016,32(12):1634-1638.
[11] Zha Y,Gan P,Liu Q,et al.TP53 codon 72 polymorphism predicts efficacy of paclitaxel plus capecitabine chemotherapy in advanced gastric cancer patients[J].Arch Med Res,2016,47(1):13-18.
[12] Sarkar C,Ralte A M,Sharma M C,et al. Recurrent astrocytic tumours-a study of TP53 immunoreactivity and malignant progression[J]. Br J Neurosurg,2002,16(4):335-342.
[13]查纪坤,舒红兵.肿瘤坏死因子信号传导的分子机理[J].中国科学c(辑),2002,32(1):1-6.
[14] Tanaka Y,Martin Mola E. IL-6 targeting compared to TNF targeting in rheumatoid arthritis:studies of olokizumab,sarilumab and sirukumab[J].Ann Rheum Dis,2014,73(9):1595-1597.
[15]陈颖,张玉芳,李奕,等.Ptgds2基因在BXD重组近交系小鼠海马组织中的遗传基因组学分析[J].江苏医药,2011,37(20):2363-2365.
[16] Riedl S J, Shi Y. Molecular mechanisms of caspase regulation during apoptosis[J].Nat Rev Mol Cell Biol,2004,5(11):897-907.