基于网络药理学探究附子温阳作用机制
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摘要
目的应用网络药理方法,探讨附子温阳作用的可能机制。方法以心力衰竭和类风湿性关节炎为疾病模型,应用中药系统药理数据库和分析平台,根据口服生物利用度(OB)和药物相似度(DL)来筛选附子的活性成分,并预测出相应靶标;经人类表型术语集(HPO)数据库检索心力衰竭和类风湿性关节炎的疾病靶标;然后在蛋白质相互作用数据库(STRING)分别构建"附子成分-潜在靶标-心力衰竭"和"附子成分-潜在靶标-类风湿性关节炎"网络,通过Cytoscape软件将上述网络可视化,再根据节点介度、紧密度和连接度分别得到上述两个疾病网络的关键节点,借助GATHER数据库平台对关键节点进行京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)的基因功能富集分析。结果 "附子成分-潜在靶标-心力衰竭"网络包含146个节点,关键节点53个;"附子成分-潜在靶标-类风湿性关节炎"网络包含26个节点,关键节点10个;附子与心力衰竭相关的KEGG通路2条,与类风湿性关节炎相关的KEGG通路3条;两种疾病的共同通路为前列腺素(Prostaglandins,PGs)代谢通路和白三烯(Leukotrienes,LTs)代谢通路。结论经网络药理学测算,附子温阳的作用机制可能与其影响机体的PGs、LTs代谢通路有关。
Objective To explore the possible mechanism of aconite for the warming yang effect by using network pharmacology method.Methods With heart failure and rheumatoid arthritis as disease models,the TCMSP database was used to select the aconite active ingredients and the corresponding targets by bioavailability(OB) and drug similarity(DL).At the same time,heart failure and rheumatoid arthritis diseases targets were searched by using the HPO(The Human Phenotype Ontology) database.And then "aconite component-potential target-heart failure" and "aconite component-potential target-rheumatoid arthritis" networks were constructed through STRING database.The above networks were visualized by using Cytoscape software.According to the parameters of the node degree,the closeness and link degree of node,the key nodes of the two disease networks were obtained.Finally,the key nodes were analyzed by using the GATHER database platform for KEGG(Kyoto Encyclopedia of Genes and Genomes) gene function enrichment analysis.Results The network of "aconite component-potential target-heart failure" included 146 nodes and 53 key nodes.The network of"aconite component-potential target-rheumatoid arthritis" contained 26 nodes and 10 key nodes.Two KEGG pathways were related to heart failure and three KEGG pathways were related to rheumatoid arthritis.The prostaglandin(PGs) and leukotriene(PGs) metabolic pathways were the same pathways of two diseases.Conclusion According to the results of network pharmacology research,the yang-warming mechanism of aconite may be related to the PGs and LTs metabolic pathways.
Objective To explore the possible mechanism of aconite for the warming yang effect by using network pharmacology method.Methods With heart failure and rheumatoid arthritis as disease models,the TCMSP database was used to select the aconite active ingredients and the corresponding targets by bioavailability(OB) and drug similarity(DL).At the same time,heart failure and rheumatoid arthritis diseases targets were searched by using the HPO(The Human Phenotype Ontology) database.And then "aconite component-potential target-heart failure" and "aconite component-potential target-rheumatoid arthritis" networks were constructed through STRING database.The above networks were visualized by using Cytoscape software.According to the parameters of the node degree,the closeness and link degree of node,the key nodes of the two disease networks were obtained.Finally,the key nodes were analyzed by using the GATHER database platform for KEGG(Kyoto Encyclopedia of Genes and Genomes) gene function enrichment analysis.Results The network of "aconite component-potential target-heart failure" included 146 nodes and 53 key nodes.The network of"aconite component-potential target-rheumatoid arthritis" contained 26 nodes and 10 key nodes.Two KEGG pathways were related to heart failure and three KEGG pathways were related to rheumatoid arthritis.The prostaglandin(PGs) and leukotriene(PGs) metabolic pathways were the same pathways of two diseases.Conclusion According to the results of network pharmacology research,the yang-warming mechanism of aconite may be related to the PGs and LTs metabolic pathways.
引文
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[16] 李雅楠,王均衡,殷雨晴,等.阳虚体质理论与科学实证[J].北京中医药大学学报,2017,40(11):894-897. Li YN, Wang JH, Yin YQ, et al. Theory and scientific evidence of yang-deficient constitution[J]. Journal of Beijing University of Traditional Chinese Medicine, 2017,40(11):894-897.
[17] Hair MJ, Leclerc P, Newsum EC, et al. Expression of prostaglandin E2 enzymes in the synovium of arthralgia patients at risk of developing rheumatoid arthritis and in early arthritis patients[J]. Plos One, 2015,10(7):e0133669.
[18] Yousefi B, Jadidiniaragh F, Azizi G, et al. The role of leukotrienes in immunopathogenesis of rheumatoid arthritis[J]. Japanese Journal of Rheumatology, 2014,24(2):225-235.
[19] Corriveau S, Rousseau E, Berthiaume M, et al. Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium[J]. American Journal of Obstetrics & Gynecology, 2010,203(3):266.e1-266.e7.
[20] Lange LG, Schreiner GF. Immune mechanisms of cardiac disease[J]. New England Journal of Medicine, 1994,330(16):1129-1135.
[21] Harding P, Murray DB. The contribution of prostaglandins versus prostacyclin in ventricular remodeling during heart failure[J]. Life Sciences, 2011,89(19):671-676.
[22] Pace E, Profita M, Melis M, et al. LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space[J]. Clinical & Experimental Immunology, 2010,135(3):519-527.
[23] Boissier MC, Semerano L, Challal S, et al. Rheumatoid arthritis: from autoimmunity to synovitis and joint destruction[J]. Journal of Autoimmunity, 2012,39(3):222-228.
[24] Ganesan R, Doss HM, Rasool M. Majoon ushba, a polyherbal compound ameliorates rheumatoid arthritis via regulating inflammatory and bone remodeling markers in rats[J]. Cytokine, 2016,77(3):115-126.
[2] 高衍义,刘会风,高衍生.附子理苓汤加减联合西药治疗慢性心力衰竭临床疗效观察[J]. 亚太传统医药,2018,14(8):162-164. Gao YY, Liu HF, Gao YS. Clinical observation on treatment of chronic heart failure with Fuzi-Liqi decoction combined with western medicine[J]. Asia-Pacific Traditional Medicne, 2018,14(8):162-164.
[3] 黄延芳,贺雅琪,谭剑文.破格救心汤治疗急性心力衰竭的应用探析[J].中国中医急症,2016,25(3):443-444. Huang YF, He YQ, Tang JW. The application of "Poge Jiuxin Decoction" in treating acute heart failure[J]. Journal of Emergency in Traditional Chinese Medicine, 2016,25(3):443-444.
[4] 任明彪.麻黄附子细辛汤加减联合火针治疗类风湿性关节炎寒湿痹阻证80例[J].湖南中医杂志,2016,32(5):61-62.Ren MB. Treatment of 80 cases of rheumatoid arthritis with cold and dampness syndrome by Mahuang-Fuzi-Xixin Decoction combined with fire acupuncture[J]. Hunan Journal of Traditional Chinese Medicine, 2016,32(5):61-62.
[5] 卢立军.附子八物汤加味治疗寒湿阻络型类风湿性关节炎[J].中国实验方剂学杂志,2012,18(15):290-292.Lu LJ. Fuzi-Bawu Decoction for the treatment of rheumatoid arthritis[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2012,18(15):290-292.
[6] 杜蕊,李文杰.从气血水相关探析心力衰竭中医辨治思路[J].中国中医急症,2017,26(4):742-745. Du R, Li WJ. Analysis of heart failure syndrome differentiation and treatment based on correlation of qi, blood and water[J]. China Emergency Medicine, 2017,26(4):742-745.
[7] 戴良贺,程小昱.古今名医从温阳为大法论治心衰.浙江中医药大学学报,2013,37(3):252-255. Dai LH, Cheng XY. Ancient and modern famous doctors cognition for heart failure treatment method[J]. Journal of Zhejiang Chinese Medical University, 2013,37(3):252-255.
[8] 王彦鹏,全健.温阳散寒除湿汤治疗类风湿关节炎及对血清炎症因子表达的影响[J].四川中医,2016,34(5):113-115. Wang YP, Quan J. Treatment of rheumatoid arthritis by Wenyang San Han Decoction and the effect on inflammatory factor expression in serum[J].Journal of Sichuan of Traditional Chinese Medicine, 2016,34(5):113-115.
[9] 宋江润.中医对类风湿性关节炎的认识探讨[J].中国中医急症,2008,17(4):487.Song JR. Understanding of rheumatoid arthritis in traditional Chinese medicine[J]. Journal of Emergency in Traditional Chinese Medicine, 2008,17(4):487.
[10] Tang J, Tero A. Network pharmacology strategies toward multi-target anticancer therapies: from computational models to experimental design principles[J]. Curr Pharm Des, 2014,20(1):23-36.
[11] Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines[J]. Journal of Cheminformatics, 2014,6(1):13.
[12] Kohler S, Vasilevsky NA, Engelstad M, et al. The human phenotype ontology in 2017[J]. Nucleic Acids Research, 2017,45:D865-D876.
[13] Franceschini A, Szklarczyk D, Frankild S, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration[J]. Nucleic Acids Research, 2013,41:D808-D815.
[14] Max F, Christian TL, Gerardo H, et al. Cytoscape.js: a graph theory library for visualisation and analysis[J]. Bioinformatics, 2016,32(2):309-311.
[15] Chang JT, Nevins JR. GATHER: A Systems Approach to Interpreting Genomic Signatures[M]. Oxford: Oxford University Press, 2006,22(23):2926-2933.
[16] 李雅楠,王均衡,殷雨晴,等.阳虚体质理论与科学实证[J].北京中医药大学学报,2017,40(11):894-897. Li YN, Wang JH, Yin YQ, et al. Theory and scientific evidence of yang-deficient constitution[J]. Journal of Beijing University of Traditional Chinese Medicine, 2017,40(11):894-897.
[17] Hair MJ, Leclerc P, Newsum EC, et al. Expression of prostaglandin E2 enzymes in the synovium of arthralgia patients at risk of developing rheumatoid arthritis and in early arthritis patients[J]. Plos One, 2015,10(7):e0133669.
[18] Yousefi B, Jadidiniaragh F, Azizi G, et al. The role of leukotrienes in immunopathogenesis of rheumatoid arthritis[J]. Japanese Journal of Rheumatology, 2014,24(2):225-235.
[19] Corriveau S, Rousseau E, Berthiaume M, et al. Lipoxygenase and cyclooxygenase inhibitors reveal a complementary role of arachidonic acid derivatives in pregnant human myometrium[J]. American Journal of Obstetrics & Gynecology, 2010,203(3):266.e1-266.e7.
[20] Lange LG, Schreiner GF. Immune mechanisms of cardiac disease[J]. New England Journal of Medicine, 1994,330(16):1129-1135.
[21] Harding P, Murray DB. The contribution of prostaglandins versus prostacyclin in ventricular remodeling during heart failure[J]. Life Sciences, 2011,89(19):671-676.
[22] Pace E, Profita M, Melis M, et al. LTB4 is present in exudative pleural effusions and contributes actively to neutrophil recruitment in the inflamed pleural space[J]. Clinical & Experimental Immunology, 2010,135(3):519-527.
[23] Boissier MC, Semerano L, Challal S, et al. Rheumatoid arthritis: from autoimmunity to synovitis and joint destruction[J]. Journal of Autoimmunity, 2012,39(3):222-228.
[24] Ganesan R, Doss HM, Rasool M. Majoon ushba, a polyherbal compound ameliorates rheumatoid arthritis via regulating inflammatory and bone remodeling markers in rats[J]. Cytokine, 2016,77(3):115-126.