基于网络药理学的气滞胃痛颗粒抗炎镇痛活性作用分析
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摘要
目的通过网络药理学的方法预测气滞胃痛颗粒抗炎镇痛主要活性成分的作用靶点,结合中医方解配伍理论对其多成分-多靶点-多通路的作用进行分析。方法基于TCMSP中药系统生物学分析数据库收集气滞胃痛颗粒中6味中药的主要化学成分,并借助LC-MS技术对所筛成分进行分析,通过TCMSP检索和Pharmmapper软件预测获取各成分主要的作用靶标,并通过DIP数据库,利用蛋白质相互作用信息建立药物靶标与炎症疼痛靶标的关联,构建药物-靶标-疾病网络,通过网络特征分析气滞胃痛颗粒抗炎镇痛的作用靶标,阐释其抗炎镇痛的主要作用机制。结果根据网络分析,共有44个炎症疼痛靶点与气滞胃痛颗粒密切相关,其中直接作用靶点有20个,主要是对环加氧酶-2(COX-2)和诱导型一氧化氮合酶(i NOS)等蛋白酶的作用,作用机制可能与调节肿瘤坏死因子(TNF)信号通路、NOD样受体(NLR)信号通路、血管内皮生长因子(VEGF)信号通路等与炎症疼痛密切相关的信号通路有关。结论气滞胃痛颗粒抗炎镇痛作用体现了中药多成分、多靶点、多途径的作用特点,该研究为深入阐释气滞胃痛颗粒抗炎镇痛作用机制提供科学依据,并且进一步说明了中医药古方配伍理论的科学性。
Objective The target of anti-inflammatory and analgesic active components of Qizhi Weitong Granules was predicted by network pharmacology method, and the effect of multi-component-multi-target-multi-pathways on TCM-complexation theory was analyzed. Methods The main chemical constituents of six Chinese medicines in Qizhi Weitong Granules were collected based on the TCMSP Chinese Medicine System Biological Analysis Database and analyzed by LC-MS. The main target of each component was predicted by TCMSP search and Pharmmapper software. The relationship between drug, target and inflammatory pain target was established by DIP database and protein interaction information. In order to elucidate the main mechanism of anti-inflammatory and analgesic effects of Qizhi Weitong Granules, the network of "drug-target-disease" was constructed and the target of anti-inflammatory and analgesic effects of Qizhi Weitong Granules were analyzed by network characteristics. Results Through the network analysis, a total of 44 inflammatory targets were closely related to Qizhi Weitong Granules, of which 20 were directly targeted, mainly for the action of proteases such as COX-2 and iNOS. The mechanism may be related to the regulation of TNF signaling pathway, NOD-like receptor signaling pathways, VEGF signaling pathways and other signaling pathways closely related to inflammation. Conclusion The anti-inflammatory and analgesic effects of Qizhi Weitong Granules reflect the multi-component, multi-target and multi-pathway characteristics of traditional Chinese medicine. This study provides a scientific basis for further understanding the anti-inflammatory and analgesic mechanism of Qizhi Weitong Granules and explains the scientificity of the traditional Chinese medicine compatibility theory.
Objective The target of anti-inflammatory and analgesic active components of Qizhi Weitong Granules was predicted by network pharmacology method, and the effect of multi-component-multi-target-multi-pathways on TCM-complexation theory was analyzed. Methods The main chemical constituents of six Chinese medicines in Qizhi Weitong Granules were collected based on the TCMSP Chinese Medicine System Biological Analysis Database and analyzed by LC-MS. The main target of each component was predicted by TCMSP search and Pharmmapper software. The relationship between drug, target and inflammatory pain target was established by DIP database and protein interaction information. In order to elucidate the main mechanism of anti-inflammatory and analgesic effects of Qizhi Weitong Granules, the network of "drug-target-disease" was constructed and the target of anti-inflammatory and analgesic effects of Qizhi Weitong Granules were analyzed by network characteristics. Results Through the network analysis, a total of 44 inflammatory targets were closely related to Qizhi Weitong Granules, of which 20 were directly targeted, mainly for the action of proteases such as COX-2 and iNOS. The mechanism may be related to the regulation of TNF signaling pathway, NOD-like receptor signaling pathways, VEGF signaling pathways and other signaling pathways closely related to inflammation. Conclusion The anti-inflammatory and analgesic effects of Qizhi Weitong Granules reflect the multi-component, multi-target and multi-pathway characteristics of traditional Chinese medicine. This study provides a scientific basis for further understanding the anti-inflammatory and analgesic mechanism of Qizhi Weitong Granules and explains the scientificity of the traditional Chinese medicine compatibility theory.
引文
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[12]柴煊,孟雅坤,柏兆方,等.基于生物靶标网络分析的山豆根抗乙肝病毒的作用机制初步研究[J].药学学报,2018,53(3):396-402.
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[14]Li H Y,Zhao L H,Zhang B,et al.A network pharmacology approach to determine active compounds and action mechanisms of ge-gen-qinlian decoction for treatment of type 2 diabetes[J].Evid Based Compl Alternat Med,2014,2014(1):495840.
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[16]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,2012,26(1):4-9.
[17]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[18]Ru J L,Li P,Wang J N,et al.TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminform,2014,6(1):13.
[19]Xenarios I,Rice D W,Salwinski L,et al.DIP:The database of interacting proteins[J].Nucleic Acids Res,2000,32(1):289-291.
[20]李毅,王忠,周思凤.中医辨证治疗脾胃气虚型胃痛的疗效观察[J].中医临床研究,2017,9(3):135-136.
[21]毛近隆,李晓宇,孙蓉.环氧合酶(COX-2)抑制剂提高心血管安全性的抗炎机制探讨[J].中国中药杂志,2014,(20):4054-4059.
[22]吴检,黄键.环氧合酶-2及其在炎症痛中表达的调节[J].海峡药学,2010,22(9):205-208.
[23]Kunsch C,Medford R M.Oxidative stress as a regulator of gene expression in the vasculature[J].Circ Res,1999,85(8):753-766.
[24]Grendling K K,Sorescu D,Ushio-Fukai M.NAD(P)Hoxidase:Role in cardiovascular biology and diseases[J].Circ Res,2000,86(5):494-501.
[25]夏琳生,查安生.中医药对慢性萎缩性胃炎COX-2及相关信号通路的干预研究[J].中国中西医结合消化杂志,2015,23(11):828-830.
[26]沈洁,马娅梅.COX-2及c-met蛋白在疣状胃炎与胃癌中的表达及其意义[J].广州医科大学学报,2014,30(5):102-104.
[27]吴柯,杨俊霞,周岐新.小檗碱对实验性大鼠结肠癌的防治作用与环氧化酶2关系的研究[J].中国中药杂志,2010,35(20):2768-2773.
[28]孟德胜,汪仕良.槲皮素对烫伤大鼠肠黏膜PGE2代谢的影响[J].第三军医大学学报,2002,24(10):1202-1204.
[29]冯仲锴,孙永强,刘汝银.芍药苷对大鼠脊髓损伤的神经保护机制[J].免疫学杂志,2016,32(5):376-381.
[2]孙方圆.气滞胃痛颗粒治疗功能性消化不良的脑肠轴机制研究[D].天津:天津医科大学,2017.
[3]于婷,王帅,孟宪生,包永睿,等.气滞胃痛颗粒防治反流性胃炎的药效及作用机制初步研究[J].中药材,2015,38(9):1933-1936.
[4]姚东,孟宪生,潘英,等.气滞胃痛颗粒镇痛作用研究及机制初探[J].中成药,2012,34(3):556-558.
[5]陈亚双,孙世伟.柴胡的化学成分及药理作用研究进展[J].黑龙江医药,2014,27(3):630-633.
[6]李岩.白芍及其化学成分的药理研究进展[J].职业与健康,2015,31(15):2153-2156.
[7]曹玫,张洪,张晓燕,等.香附的药理活性作用研究进展[J].药物流行病学杂志,2010,19(2):111-113.
[8]王红,田明,王淼,等.延胡索现代药理及临床研究进展[J].中医药学报,2010,38(6):108-111.
[9]章斌,金剑,金芝贵,等.枳壳的药理作用与临床应用进展[J].医药导报,2013,32(11):1462-1464.
[10]高雪岩,王文全,魏胜利,等.甘草及其活性成分的药理活性研究进展[J].中国中药杂志,2009,34(21):2695-2700.
[11]欧阳罗丹,胡小松,牛明,等.基于网络药理学的水蛭活血化瘀的作用机制研究[J].中国中药杂志,2018,43(9):1901-1906.
[12]柴煊,孟雅坤,柏兆方,等.基于生物靶标网络分析的山豆根抗乙肝病毒的作用机制初步研究[J].药学学报,2018,53(3):396-402.
[13]Sheng S,Wang J,Wang L,et al.Network pharmacology analyses of the antithrombotic pharmacological mechanism of Fufang Xueshuantong Capsule with experimental support using disseminated intravascular coagulation rats[J].J Ethnopharmacol,2014,154(3):735-744.
[14]Li H Y,Zhao L H,Zhang B,et al.A network pharmacology approach to determine active compounds and action mechanisms of ge-gen-qinlian decoction for treatment of type 2 diabetes[J].Evid Based Compl Alternat Med,2014,2014(1):495840.
[15]严诗楷,赵静,窦圣姗,等.基于系统生物学与网络生物学的现代中药复方研究体系[J].中国天然药物,2009,7(4):249-259.
[16]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,2012,26(1):4-9.
[17]李梢.网络靶标:中药方剂网络药理学研究的一个切入点[J].中国中药杂志,2011,36(15):2017-2020.
[18]Ru J L,Li P,Wang J N,et al.TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminform,2014,6(1):13.
[19]Xenarios I,Rice D W,Salwinski L,et al.DIP:The database of interacting proteins[J].Nucleic Acids Res,2000,32(1):289-291.
[20]李毅,王忠,周思凤.中医辨证治疗脾胃气虚型胃痛的疗效观察[J].中医临床研究,2017,9(3):135-136.
[21]毛近隆,李晓宇,孙蓉.环氧合酶(COX-2)抑制剂提高心血管安全性的抗炎机制探讨[J].中国中药杂志,2014,(20):4054-4059.
[22]吴检,黄键.环氧合酶-2及其在炎症痛中表达的调节[J].海峡药学,2010,22(9):205-208.
[23]Kunsch C,Medford R M.Oxidative stress as a regulator of gene expression in the vasculature[J].Circ Res,1999,85(8):753-766.
[24]Grendling K K,Sorescu D,Ushio-Fukai M.NAD(P)Hoxidase:Role in cardiovascular biology and diseases[J].Circ Res,2000,86(5):494-501.
[25]夏琳生,查安生.中医药对慢性萎缩性胃炎COX-2及相关信号通路的干预研究[J].中国中西医结合消化杂志,2015,23(11):828-830.
[26]沈洁,马娅梅.COX-2及c-met蛋白在疣状胃炎与胃癌中的表达及其意义[J].广州医科大学学报,2014,30(5):102-104.
[27]吴柯,杨俊霞,周岐新.小檗碱对实验性大鼠结肠癌的防治作用与环氧化酶2关系的研究[J].中国中药杂志,2010,35(20):2768-2773.
[28]孟德胜,汪仕良.槲皮素对烫伤大鼠肠黏膜PGE2代谢的影响[J].第三军医大学学报,2002,24(10):1202-1204.
[29]冯仲锴,孙永强,刘汝银.芍药苷对大鼠脊髓损伤的神经保护机制[J].免疫学杂志,2016,32(5):376-381.