“丹参-三七”药对作用机制的网络药理学探讨
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摘要
目的:探讨"丹参-三七"药对的物质基础,预测其作用方向。方法:在中药系统药理学分析平台(TCMSP)检索"丹参"和"三七"所有的分子、靶点和相关疾病,使用cytoscape 3.2.1软件构建"活性成分-作用靶点"和"作用靶点-相关疾病"的网络模型,对药对物质基础和机制进行预测和研究。结果:通过口服利用度(oral bioavailability,OB)和类药性(drug-likeness,DL)筛选得到73个活性成分,145个靶点和325中相关疾病。自由度(degree)值较高的活性成分有槲皮素(87),β-谷固醇(51)和1,2,5,6-四氢丹参酮(46)等,degree值较高的靶点有雌激素受体(63),雄激素受体(59),前列腺素G/H合成酶2(56)等,Degree值较高的疾病有癌(16),肺转移性骨肉瘤(12),心血管疾病(10),乳腺癌(9)和胰腺癌(9)等。结论:该文对"丹参-三七"药对的物质基础和机制进行初步预测,为更深层次的研究和临床提供思考方向。
Objective: To investigate the material basis and predict the direction of action of Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma paired drugs. Method: All the molecules,targets and related diseases for Salviae Miltiorrhizae Radix et Rhizoma and Notoginseng Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 software was used to build the ‘active ingredient-target'and ‘target-related diseases' network model,and then the material basis and mechanism were studied and predicted. Result: Totally 73 active components,145 targets and 325 related diseases were screened through oral bioavailability( OB) and drug likeness( DL)conditions. The first three active components with higher degree value included quercetin( 87),beta-sitosterol( 51) and 1,2,5,6-tetrahydrotanshinone( 46). The first three targets with higher degree value included estrogen receptor( 63),androgen receptor( 59),and prostaglandin-endoperoxide synthase 2( 56). The related diseases with higher degree value included cancer( 16),metastatic osteosarcoma in the lung( 12),cardiovascular disease( 10),breast cancer( 9) and pancreatic cancer( 9),etc. Conclusion: In this paper,the material basis and mechanism of Salviae Miltiorrhizae Radix et Rhizoma Notoginseng Radix et Rhizoma paired drugs were preliminarily predicted,providing a thinking direction for further research and clinical application.
Objective: To investigate the material basis and predict the direction of action of Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma paired drugs. Method: All the molecules,targets and related diseases for Salviae Miltiorrhizae Radix et Rhizoma and Notoginseng Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform( TCMSP). Cytoscape3. 2. 1 software was used to build the ‘active ingredient-target'and ‘target-related diseases' network model,and then the material basis and mechanism were studied and predicted. Result: Totally 73 active components,145 targets and 325 related diseases were screened through oral bioavailability( OB) and drug likeness( DL)conditions. The first three active components with higher degree value included quercetin( 87),beta-sitosterol( 51) and 1,2,5,6-tetrahydrotanshinone( 46). The first three targets with higher degree value included estrogen receptor( 63),androgen receptor( 59),and prostaglandin-endoperoxide synthase 2( 56). The related diseases with higher degree value included cancer( 16),metastatic osteosarcoma in the lung( 12),cardiovascular disease( 10),breast cancer( 9) and pancreatic cancer( 9),etc. Conclusion: In this paper,the material basis and mechanism of Salviae Miltiorrhizae Radix et Rhizoma Notoginseng Radix et Rhizoma paired drugs were preliminarily predicted,providing a thinking direction for further research and clinical application.
引文
[1]耿燕娜,张文鑫.一测多评法同时测定复方丹参片中人参皂苷Rg1,Re,Rb1和三七皂苷R1含量[J].中国实验方剂学杂志,2015,21(1):69-72.
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[6]ZHANG J P,ZHANG Y Y,ZHANG Y,et al.Salvia miltiorrhiza(Danshen)injection ameliorates iron overload-induced cardiac damage in mice[J].Planta Med,2013,79(9):744-752.
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[8]XIE Z,Truong T L,ZHANG P,et al.Dan-Qi prescription ameliorates insulin resistance through overall corrective regulation of glucose and fat metabolism[J].J Ethnopharmacol,2015,172:70-79.
[9]ZHOU X,Razmovski-Naumovski V,CHANG D,et al.Synergistic effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)combination in inhibiting inflammation mediators in RAW264.7 cells[J].Biomed Res Int,2016,2016:5758195.
[10]赖玉玲,黄丽芳,卢建华,等.脂代谢指标联合血清CEA,CA19-9检测对诊断结直肠癌的临床意义[J].中国医学创新,2017,14(35):74-77.
[11]莫淋,顾军.糖代谢异常与乳腺癌的关系[J].肠外与肠内营养,2015,22(4):240-243.
[12]陈晓秋,李柱,胡阳春,等.消化道恶性肿瘤患者营养风险、营养状况与炎症因子的相关性及其对临床结局的影响[J].广东医学,2015,36(10):1505-1508.
[13]吴嘉瑞,金燕萍,王凯欢,等.基于网络药理学的“金银花-连翘”药对作用机制分析[J].中国实验方剂学杂志,2017,23(5):179-183.
[14]吴嘉瑞,金燕萍,段笑娇,等.基于网络药理学的“桔梗-甘草”药对作用机制分析[J].中国实验方剂学杂志,2017,23(5):184-188.
[15]SHI H B,CHEN J D,CHEN X H,et al.Effects of salvianolic acid and notoginseng triterpenes on angiogenesis in EA-hy926 cells in vitro[J].Chin J Nat Med,2013,11(3):254-257.
[16]CHEN W,QIU Y.Ginsenoside Rh2 targets EGFR by up-regulation of miR-491 to enhance anti-tumor activity in hepatitis B virus-related hepatocellular carcinoma[J].Cell Biochem Biophys,2015,72(2):325-331.
[17]LI L C,PIAO H M,ZHENG M Y,et al.Ginsenoside Rh2 attenuates allergic airway inflammation by modulating nuclear factor-κB activation in a murine model of asthma[J].Mol Med Rep,2015,12(5):6946-6954.
[18]HOU J,XUE J,Lee M,et al.Ginsenoside Rh2improves learning and memory in mice[J].J Med Food,2013,16(8):772-776.
[19]GUO Y,LI Y,XUE L,et al.Salvia miltiorrhiza:an ancient Chinese herbal medicine as a source for antiosteoporotic drugs[J].J Ethnopharmacol,2014,155(3):1401-1416.
[20]XU G,HOU A J,ZHENG Y T,et al.Przewalskin B,a novel diterpenoid with an unprecedented skeleton from Salvia przewalskii maxim[J].Org Lett,2007,9(2):291-293.
[21]周志远,卢群,刘洋,等.豆甾醇的研究及开发进展[J].中国当代医药,2015,22(24):15-17.
[22]王敏,刘保林,国旭丹.槲皮素及其代谢物抑制氧化应激与炎症[J].食品科学,2013,34(15):256-260.
[23]孙怡,顾君.槲皮素抑制乳腺癌细胞迁移侵袭及分子机制研究[J].中国中药杂志,2015,40(6):1144-1150.
[24]谢辛慈,吴佳,潘芬芬,等.雌激素受体与肿瘤发生的研究进展[J].药物生物技术,2015,22(2):156-159.
[25]吴双双,吴建辉,孙祖越.前列腺素合成酶基因调控与前列腺疾病关系的研究进展[J].中华男科学杂志,2017,23(7):663-667.
[26]刘春琳,李永强,胡晓桦,等.前列腺素内过氧化物合成酶2基因单核苷酸多态性与原发性肝癌预后关系的研究[J].广西医学,2014,36(10):1366-1370.
[27]臧桐,孙凤岭,李瑛,等.前列腺素合成酶-2在膀胱癌中的表达[J].中华泌尿外科杂志,2002,7(3):158.
[28]崔百日,卞超超,洪兰,等.缺氧条件下L型前列腺素D合成酶对内皮素1调控ANP分泌作用的影响[J].中国病理生理杂志,2015,31(10):1792.
[29]CHANG Y,ZHANG W,XIE Y,et al.Postmarketing safety evaluation:depside salt injection made from Danshen(Radix Salviae Miltiorrhizae)[J].J Tradit Chin Med,2014,34(6):749-753.
[30]GUAN S,MA J,ZHANG Y,et al.Danshen(Salvia miltiorrhiza)injection suppresses kidney injury induced by iron overload in mice[J].PLo S One,2013,8(9):e74318.
[31]LONG W,ZHANG S C,WEN L,et al.In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration[J].J Ethnopharmacol,2014,156:199-208.
[32]徐玉玲,白婷钰,付春梅,等.三七配伍丹参对丹参中成分提取溶出的影响[J].中草药,2016,47(24):4357-4363.
[2]王玉龙,吕光耀,王娅妮,等.基于1H-NMR的丹七片对自发性高血压大鼠尿液代谢组学分析[J].中国实验方剂学杂志,2017,23(4):102-107.
[3]ZHOU G J,WANG W,XIE X M,et al.Post-harvest induced production of salvianolic acids and significant promotion of antioxidant properties in roots of Salvia miltiorrhiza(Danshen)[J].Molecules,2014,19(6):7207-7222.
[4]ZHANG X,WU J,ZHANG B.Xuesaitong injection as one adjuvant treatment of acute cerebral infarction:a systematic review and Meta-analysis[J].BMC Complement Altern Med,2015,15(1):36.
[5]LIAN F,WU L,TIAN J,et al.The effectiveness and safety of a danshen-containing Chinese herbal medicine for diabetic retinopathy:a randomized,double-blind,placebo-controlled multicenter clinical trial[J].J Ethnopharmacol,2015,164:71-77.
[6]ZHANG J P,ZHANG Y Y,ZHANG Y,et al.Salvia miltiorrhiza(Danshen)injection ameliorates iron overload-induced cardiac damage in mice[J].Planta Med,2013,79(9):744-752.
[7]QIN R A,LIN J,LI C Y,et al.Study of the protective mechanisms of compound Danshen tablet(Fufang Danshen pian)against myocardial ischemia/reperfusion injury via the Akt-e NOS signaling pathway in rats[J].J Ethnopharmacol,2014,156(1):190-198.
[8]XIE Z,Truong T L,ZHANG P,et al.Dan-Qi prescription ameliorates insulin resistance through overall corrective regulation of glucose and fat metabolism[J].J Ethnopharmacol,2015,172:70-79.
[9]ZHOU X,Razmovski-Naumovski V,CHANG D,et al.Synergistic effects of Danshen(Salvia Miltiorrhiza Radix et Rhizoma)and Sanqi(Notoginseng Radix et Rhizoma)combination in inhibiting inflammation mediators in RAW264.7 cells[J].Biomed Res Int,2016,2016:5758195.
[10]赖玉玲,黄丽芳,卢建华,等.脂代谢指标联合血清CEA,CA19-9检测对诊断结直肠癌的临床意义[J].中国医学创新,2017,14(35):74-77.
[11]莫淋,顾军.糖代谢异常与乳腺癌的关系[J].肠外与肠内营养,2015,22(4):240-243.
[12]陈晓秋,李柱,胡阳春,等.消化道恶性肿瘤患者营养风险、营养状况与炎症因子的相关性及其对临床结局的影响[J].广东医学,2015,36(10):1505-1508.
[13]吴嘉瑞,金燕萍,王凯欢,等.基于网络药理学的“金银花-连翘”药对作用机制分析[J].中国实验方剂学杂志,2017,23(5):179-183.
[14]吴嘉瑞,金燕萍,段笑娇,等.基于网络药理学的“桔梗-甘草”药对作用机制分析[J].中国实验方剂学杂志,2017,23(5):184-188.
[15]SHI H B,CHEN J D,CHEN X H,et al.Effects of salvianolic acid and notoginseng triterpenes on angiogenesis in EA-hy926 cells in vitro[J].Chin J Nat Med,2013,11(3):254-257.
[16]CHEN W,QIU Y.Ginsenoside Rh2 targets EGFR by up-regulation of miR-491 to enhance anti-tumor activity in hepatitis B virus-related hepatocellular carcinoma[J].Cell Biochem Biophys,2015,72(2):325-331.
[17]LI L C,PIAO H M,ZHENG M Y,et al.Ginsenoside Rh2 attenuates allergic airway inflammation by modulating nuclear factor-κB activation in a murine model of asthma[J].Mol Med Rep,2015,12(5):6946-6954.
[18]HOU J,XUE J,Lee M,et al.Ginsenoside Rh2improves learning and memory in mice[J].J Med Food,2013,16(8):772-776.
[19]GUO Y,LI Y,XUE L,et al.Salvia miltiorrhiza:an ancient Chinese herbal medicine as a source for antiosteoporotic drugs[J].J Ethnopharmacol,2014,155(3):1401-1416.
[20]XU G,HOU A J,ZHENG Y T,et al.Przewalskin B,a novel diterpenoid with an unprecedented skeleton from Salvia przewalskii maxim[J].Org Lett,2007,9(2):291-293.
[21]周志远,卢群,刘洋,等.豆甾醇的研究及开发进展[J].中国当代医药,2015,22(24):15-17.
[22]王敏,刘保林,国旭丹.槲皮素及其代谢物抑制氧化应激与炎症[J].食品科学,2013,34(15):256-260.
[23]孙怡,顾君.槲皮素抑制乳腺癌细胞迁移侵袭及分子机制研究[J].中国中药杂志,2015,40(6):1144-1150.
[24]谢辛慈,吴佳,潘芬芬,等.雌激素受体与肿瘤发生的研究进展[J].药物生物技术,2015,22(2):156-159.
[25]吴双双,吴建辉,孙祖越.前列腺素合成酶基因调控与前列腺疾病关系的研究进展[J].中华男科学杂志,2017,23(7):663-667.
[26]刘春琳,李永强,胡晓桦,等.前列腺素内过氧化物合成酶2基因单核苷酸多态性与原发性肝癌预后关系的研究[J].广西医学,2014,36(10):1366-1370.
[27]臧桐,孙凤岭,李瑛,等.前列腺素合成酶-2在膀胱癌中的表达[J].中华泌尿外科杂志,2002,7(3):158.
[28]崔百日,卞超超,洪兰,等.缺氧条件下L型前列腺素D合成酶对内皮素1调控ANP分泌作用的影响[J].中国病理生理杂志,2015,31(10):1792.
[29]CHANG Y,ZHANG W,XIE Y,et al.Postmarketing safety evaluation:depside salt injection made from Danshen(Radix Salviae Miltiorrhizae)[J].J Tradit Chin Med,2014,34(6):749-753.
[30]GUAN S,MA J,ZHANG Y,et al.Danshen(Salvia miltiorrhiza)injection suppresses kidney injury induced by iron overload in mice[J].PLo S One,2013,8(9):e74318.
[31]LONG W,ZHANG S C,WEN L,et al.In vivo distribution and pharmacokinetics of multiple active components from Danshen and Sanqi and their combination via inner ear administration[J].J Ethnopharmacol,2014,156:199-208.
[32]徐玉玲,白婷钰,付春梅,等.三七配伍丹参对丹参中成分提取溶出的影响[J].中草药,2016,47(24):4357-4363.