基于网络药理学方法探讨四妙勇安汤治疗动脉粥样硬化的作用机制
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摘要
目的:通过网络药理学方法探讨四妙勇安汤治疗动脉粥样硬化的作用机制。方法:从中药系统药理学分析平台(TCMSP)中寻找与四妙勇安汤中四味中药相关的所有化学成分和作用靶点,构建化合物靶点相互作用网络图;通过OMIM数据库,TTD数据库以及PharmGkb数据库筛选动脉粥样硬化相关的靶点,进而构建疾病靶点相互作用网络图;筛选药物靶点和疾病靶点相互作用图的核心靶点,利用ClueGO对核心靶点进行GO分析,利用KEGG数据库对核心靶点进行相关通路富集。结果:选择口服利用度(OB)≥30%,类药性(DL)≥0.18作为化合物分子的筛选条件,筛选出四妙勇安汤132个活性成分和163个相应蛋白靶点;通过度、介度中心度、接近中心度等网络拓扑特征评价筛选出与四妙勇安汤在动脉粥样硬化方面作用核心靶点196个,GO分析共包含117条富集结果,其中生物过程77条,分子功能23条,细胞组成17条。利用KEGG数据库对入选靶标进行相关通路富集,筛选出20条通路在动脉粥样硬化方面具有作用。结论:通过网络药理学证实了四妙勇安汤多成分、多靶点、整体调节的作用特点,预测了四妙勇安汤治疗动脉粥样硬化的主要可能的作用机制,为其活性成分研究和实验研究提供理论依据。
Objective: Network pharmacology method was adopted in this study to explore the active compounds and mechanism of SimiaoYong'an Decoction for atherosclerosis.Method:Chemical components and targets related to the herbs in SimiaoYong'an Decoction were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Compound-target networkwas constructed to explore the mechanism of SimiaoYong'an Decoction.Through OMIM database, TTD database and PharmGkb database, the target of atherosclerosis was selected, and then the network diagram of disease target interaction was constructedto screen the nuclear target of drug target and disease target interaction diagram. ClueGO was used to carry out GO analysis of the nuclear target, and the KEGG database to carry on the related pathway enrichment of the nuclear target.Results:According to the oral bioavailability(OB) greater than 30% and drug likeness(DL) conditionsmore than 0.18,132 active ingredients and 163 corresponding protein targets were selected out. Through the evaluation of network topological characteristics, such as degree, medium degree, and proximity to the center, 196 targets were selected to serve as the nuclear target in atherosclerosis. There were 117 gene ontology(GO) entries,including 77 biological process entries,23 function entries and 17 cell component entries.The KEGG database was used for the enrichment of the selected targets, and 20 pathways were selected to play a role. Conclusion: This study revealed the main active compounds and possible mechanism of SimiaoYong'an Decoction for treatment of atherosclerosis. And meanwhile,it verified the characteristics of multi-components,multi-targets and integral regulation for SimiaoYong'an Decoction,predicting the main possible mechanism for the treatment of atherosclerosis and providing the theoretical basis for the study of active ingredients and experimental research.
Objective: Network pharmacology method was adopted in this study to explore the active compounds and mechanism of SimiaoYong'an Decoction for atherosclerosis.Method:Chemical components and targets related to the herbs in SimiaoYong'an Decoction were searched through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Compound-target networkwas constructed to explore the mechanism of SimiaoYong'an Decoction.Through OMIM database, TTD database and PharmGkb database, the target of atherosclerosis was selected, and then the network diagram of disease target interaction was constructedto screen the nuclear target of drug target and disease target interaction diagram. ClueGO was used to carry out GO analysis of the nuclear target, and the KEGG database to carry on the related pathway enrichment of the nuclear target.Results:According to the oral bioavailability(OB) greater than 30% and drug likeness(DL) conditionsmore than 0.18,132 active ingredients and 163 corresponding protein targets were selected out. Through the evaluation of network topological characteristics, such as degree, medium degree, and proximity to the center, 196 targets were selected to serve as the nuclear target in atherosclerosis. There were 117 gene ontology(GO) entries,including 77 biological process entries,23 function entries and 17 cell component entries.The KEGG database was used for the enrichment of the selected targets, and 20 pathways were selected to play a role. Conclusion: This study revealed the main active compounds and possible mechanism of SimiaoYong'an Decoction for treatment of atherosclerosis. And meanwhile,it verified the characteristics of multi-components,multi-targets and integral regulation for SimiaoYong'an Decoction,predicting the main possible mechanism for the treatment of atherosclerosis and providing the theoretical basis for the study of active ingredients and experimental research.
引文
[1] 李萌.清热解毒活血法——四妙勇安汤稳定动脉粥样硬化斑块的理论与实验研究[D].天津:天津中医药大学,2017.
[2] 薛刚,韩旭.四妙勇安汤防治冠心病的研究进展[J].湖南中医杂志,2015,31(4):183-184.
[3] 张淑芹,范志涛,刘翠文.四妙勇安汤合失笑散治疗急性心肌梗死疗效观察[J].中西医结合心脑血管病杂志,2013,11(5):535-537.
[4] 刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,47(6):696-703.
[5] 张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
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[10] 李尚珠,黄平平,金永娟,等.阿魏酸钠对闭塞性动脉硬化症患者白细胞自发活化及表面黏附分子表达的影响[J].中国中西医结合杂志,2001(7):492-494.
[11] Mendes-Silva W, Assafim M, Ruta B, et al.Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor[J].Thromb Res,2003,112(1-2):93-98.
[12] 刘鑫馗,吴嘉瑞,蔺梦娟,等.基于网络药理学的四君子汤作用机制分析[J].中国实验方剂学杂志,2017,23(16):194-202.
[13] Ueda K, Lu Q, Baur W, et al.Rapid estrogen receptor signaling mediates estrogen-induced inhibition of vascular smooth muscle cell proliferation[J].Arterioscler Thromb Vasc Biol,2013,33(8):1837-143.
[14] Nakamura Y, Suzuki T, Miki Y, et al.Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular smooth muscle cell proliferation by estrogens[J].Mol Cell Endocrinol,2004,219(1-2):17-26.
[15] 刘惠. 基于系统药理学的甘草作用机制和新药发现研究[D].咸阳:西北农林科技大学,2013.
[16] 石健,侯静波.基质金属蛋白酶与动脉粥样硬化关系研究新进展[J].国际心血管病杂志,2013,40(1):25-27,52.
[17] 郭爱桃,韦立新,石怀银,等.基质金属蛋白酶1与冠状动脉粥样硬化斑块破裂的关系[J].中华病理学杂志,2000(4):21-24.
[18] 张军平,许颖智,李明,等.四妙勇安汤对动脉粥样硬化模型兔氧化应激及炎症反应的影响[J].中医杂志,2010,51(1):72-74.
[19] 张军平,李明,李良军,等.四妙勇安汤调控核因子-κB活性及抑制相关炎症因子的实验研究[J].中华中医药杂志,2010,25(3):372-376.
[20] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化易损斑块内细胞外基质的影响[J].中华中医药杂志,2011,26(4):822-824.
[21] 杨萃, 袁卓, 张军平.四妙勇安汤对血管平滑肌细胞迁移的影响[J].中华中医药杂志,2013(5):1480-1483.
[22] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化易损斑块内细胞外基质的影响[J].中华中医药杂志,2011,26(4):822-824.
[23] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化斑块易损指数的影响及机制探讨[J].中华中医药杂志,2010,25(12):2298-2301.
[2] 薛刚,韩旭.四妙勇安汤防治冠心病的研究进展[J].湖南中医杂志,2015,31(4):183-184.
[3] 张淑芹,范志涛,刘翠文.四妙勇安汤合失笑散治疗急性心肌梗死疗效观察[J].中西医结合心脑血管病杂志,2013,11(5):535-537.
[4] 刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,47(6):696-703.
[5] 张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[6] TaeJ,Han S,Yoo J,et al.Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema[J].Clin Chim Acta,2003,330(1-2):165-171.
[7] 王强,陈东辉,邓文龙.金银花提取物对血脂与血糖的影响[J].中药药理与临床,2007(3):40-42.
[8] 李静,陈长勋,高阳,等.玄参提取物抗炎与抗动脉硬化作用的探索[J].时珍国医国药,2010,21(3):532-534.
[9] 崔忠生,邸科前,马焕云.哈巴苷及哈巴俄苷对过氧化氢损伤血管内皮细胞的保护作用[J].医学研究与教育,2009,26(2):11-12.
[10] 李尚珠,黄平平,金永娟,等.阿魏酸钠对闭塞性动脉硬化症患者白细胞自发活化及表面黏附分子表达的影响[J].中国中西医结合杂志,2001(7):492-494.
[11] Mendes-Silva W, Assafim M, Ruta B, et al.Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor[J].Thromb Res,2003,112(1-2):93-98.
[12] 刘鑫馗,吴嘉瑞,蔺梦娟,等.基于网络药理学的四君子汤作用机制分析[J].中国实验方剂学杂志,2017,23(16):194-202.
[13] Ueda K, Lu Q, Baur W, et al.Rapid estrogen receptor signaling mediates estrogen-induced inhibition of vascular smooth muscle cell proliferation[J].Arterioscler Thromb Vasc Biol,2013,33(8):1837-143.
[14] Nakamura Y, Suzuki T, Miki Y, et al.Estrogen receptors in atherosclerotic human aorta: inhibition of human vascular smooth muscle cell proliferation by estrogens[J].Mol Cell Endocrinol,2004,219(1-2):17-26.
[15] 刘惠. 基于系统药理学的甘草作用机制和新药发现研究[D].咸阳:西北农林科技大学,2013.
[16] 石健,侯静波.基质金属蛋白酶与动脉粥样硬化关系研究新进展[J].国际心血管病杂志,2013,40(1):25-27,52.
[17] 郭爱桃,韦立新,石怀银,等.基质金属蛋白酶1与冠状动脉粥样硬化斑块破裂的关系[J].中华病理学杂志,2000(4):21-24.
[18] 张军平,许颖智,李明,等.四妙勇安汤对动脉粥样硬化模型兔氧化应激及炎症反应的影响[J].中医杂志,2010,51(1):72-74.
[19] 张军平,李明,李良军,等.四妙勇安汤调控核因子-κB活性及抑制相关炎症因子的实验研究[J].中华中医药杂志,2010,25(3):372-376.
[20] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化易损斑块内细胞外基质的影响[J].中华中医药杂志,2011,26(4):822-824.
[21] 杨萃, 袁卓, 张军平.四妙勇安汤对血管平滑肌细胞迁移的影响[J].中华中医药杂志,2013(5):1480-1483.
[22] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化易损斑块内细胞外基质的影响[J].中华中医药杂志,2011,26(4):822-824.
[23] 许颖智,张军平,李明,等.四妙勇安汤对动脉粥样硬化斑块易损指数的影响及机制探讨[J].中华中医药杂志,2010,25(12):2298-2301.