基于药性组合的姜黄、郁金、莪术的性效关系研究
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摘要
姜黄、郁金、莪术均来源于姜科植物,为同一植物的不同药用部分,但三者药性不同,从而产生的功效、针对的症状亦不相同,姜黄、莪术的药性组合均为温辛肝、温苦肝,郁金的药性组合为寒心肝、寒苦肝、寒辛心、寒苦心,对比分析郁金与姜黄、莪术的性效关系的相关性和差异性,阐释三者作用机制的异同点。该文以姜黄、郁金、莪术为研究载体,通过TCMD,TCMSP,Ch EMBL数据库获取其有效成分及作用靶点,构建蛋白互作网络,对网络进行模块聚类分析。姜黄、郁金的对比研究表明,姜黄性温,通过P2RY12,GNG2等基因调节血液凝固发挥通经止痛功效;郁金性寒,通过LDLR,APOB,PRKCA,SOD1,TP53等基因调节脂质代谢、血浆脂蛋白水平、血小板活化、氧化应激反应、凋亡等过程发挥清心凉血的功效。姜黄、郁金的对比研究表明,莪术性温,通过GRIA2,GRIA4等基因调节神经系统过程发挥其破血逐瘀的功效;郁金性寒,通过CALM1,LPL,APOB,SOD1,TP53等基因调节血小板活化、脂质代谢、血浆脂蛋白、氧化应激、凋亡过程发挥清心凉血的功效。姜黄、郁金、莪术三者均为辛苦味,归肝经,其活血功效可能与参与脂质代谢、血液凝固、血红蛋白、血小板脱粒等过程有关。通过对3味中药的网络进行聚类分析,有利于阐释药性组合与功效的内在联系,为药性与功效规律的研究奠定基础。
Curcumae Longae Rhizoma,Curcumae Radix and Curcumae Rhizoma are different medicinal parts of the same plant.Nevertheless,they are different in medicinal effects due to the different Chinese herbal nature. In this study,traditional Chinese medicines database( TCMD2009),traditional Chinese medicine system( TCMSP),and Ch EMBL database were retrieved to screen the active components and targets,and construct the target PPI network. By a graph theoretic clustering algorithm identifying protein complex algorithm( IPCA),the protein modules were identified and analyzed by gene ontology( GO) enrichment. A comparative study of Curcumae Longae Rhizoma and Curcumae Radix illustrate that Curcumae Longae Rhizoma regulates blood coagulation through P2 RY12,GNG2 and other genes to exert the analgesic effect. Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process through LDLR,APOB,PRKCA,SOD1,TP53 and other genes to perform a function in clearing the heart and cooling the blood. A comparative study of Curcumae Radix and Curcumae Rhizoma demonstrate that Curcumae Rhizoma on regulates the nervous system by GRIA2,GRIA4 and other genes to exert blood-breaking effect; Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process by genes such as CALM1,LPL,APOB,SOD1 and TP53 to play the role of clearing heart and cooling blood. Cluster analysis of the protein interaction network of the nature combination is helpful to explain the intrinsic link between the nature combination and efficacy.
Curcumae Longae Rhizoma,Curcumae Radix and Curcumae Rhizoma are different medicinal parts of the same plant.Nevertheless,they are different in medicinal effects due to the different Chinese herbal nature. In this study,traditional Chinese medicines database( TCMD2009),traditional Chinese medicine system( TCMSP),and Ch EMBL database were retrieved to screen the active components and targets,and construct the target PPI network. By a graph theoretic clustering algorithm identifying protein complex algorithm( IPCA),the protein modules were identified and analyzed by gene ontology( GO) enrichment. A comparative study of Curcumae Longae Rhizoma and Curcumae Radix illustrate that Curcumae Longae Rhizoma regulates blood coagulation through P2 RY12,GNG2 and other genes to exert the analgesic effect. Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process through LDLR,APOB,PRKCA,SOD1,TP53 and other genes to perform a function in clearing the heart and cooling the blood. A comparative study of Curcumae Radix and Curcumae Rhizoma demonstrate that Curcumae Rhizoma on regulates the nervous system by GRIA2,GRIA4 and other genes to exert blood-breaking effect; Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process by genes such as CALM1,LPL,APOB,SOD1 and TP53 to play the role of clearing heart and cooling blood. Cluster analysis of the protein interaction network of the nature combination is helpful to explain the intrinsic link between the nature combination and efficacy.
引文
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[21]孟文婷,李东翔,佟玲.缺血性脑卒中的治疗研究进展[J].中国新药杂志,2016,25(10):1114.
[22]黄瑀莘,王柳萍,吴桂甫,等.莪术对局灶性脑缺血模型大鼠的神经保护作用[J].广西医科大学学报,2015,32(6):883.
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[24]何洁英,王汝上,何洁宝,等.郁金醇提取物对过氧化氢诱导的人脐静脉内皮细胞氧化应激损伤的保护作用[J].中国实验方剂学杂志,2013,19(3):223.
[25] Sasaki Y,Goto H,Tohda C,et al. Effects of curcuma drugs on vasomotion in isolated rat aorta[J]. Biol Pharm Bull,2003,26(8):1135.
[26]黎鹏程,程丑夫.论痰瘀是冠状动脉脂质斑块的主要病理基础[J].中医药导报,2012,18(7):5.
[27]邹永伟,邹华伟,牟春平.糖化血红蛋白异常与冠心病的相关性研究进展[J].中国老年学,2015,35(2):560.
[28]贝俊杰,孟璟.血小板微粒与心血管疾病[J].中国动脉硬化杂志,2013,21(9):849.
[29]马丽芬,苏振丽,王文科,等.姜黄素对2型糖尿病肾病模型大鼠肾脏氧化应激以及脂质代谢的保护作用[J].中国老年学杂志,2017,37(9):2128.
[30]王文祥,熊晓滨,毛卫红.姜黄素对高脂血症兔血液流变学、血小板聚集、抗氧化以及纤溶系统的影响[J].中国现代应用药学,2013,30(6):598.
[31]曾克武,屠鹏飞.固相亲合载体应用于中药复杂体系直接作用靶点研究的现状与挑战[J].中国中药杂志,2017,42(19):3645.
[32] Derry M M,Somasagara R,Raina K,et al. Target identification of grape seed extract in colorectal cancer using drug affinity responsive target stability(DARTS)technique:role of endoplasmic reticulum stress response proteins[J]. Curr Cancer Drug Targets,2014,14(4):323.
[2]魏志成,童东,杨娟,等.基于网络药理学的沙棘总黄酮治疗心肌缺血的作用机制研究[J].中国中药杂志,2017,42(7):1238.
[3]刘海波,乔颖欣,刘冰,等.中药化学数据库的数据仓库改造[J].中国药学杂志,2006,41(9):645.
[4]王社利,安秀群.姜黄、郁金、莪术的比较[J].陕西中医,2004,25(5):454.
[5]彭炳先,周欣,王道平,等. HPLC法测定姜黄、莪术、郁金中三种姜黄色素的含量[J].中药材,2004,27(11):813.
[6]王颖,郭兰萍,黄璐琦,等.姜黄、莪术、郁金的化学成分与药理作用研究进展[J].中国药房,2013,24(35):3338.
[7]尹国平,张清哲,安月伟,等.温郁金化学成分及药理活性研究进展[J].中国中药杂志,2012,37(22):3354.
[8] Gaulton A,Bellis L J,Bento A P,et al. ChEMBL:a large-scale bioactivity database for drug discovery[J]. Nucleic Acids Res,2012,40(Database issue):1100.
[9] Franz M,Lopes C T,Huck G,et al. Cytoscape.js:a graph theory library for visualisation and analysis[J]. Bioinformatics,2016,32(2):309.
[10] Szklarczyk D,Franceschini A,Wyder S,et al. STRING v10:protein-protein interaction networks,integrated over the tree of life[J]. Nucleic Acids Res,2015,43:D447.
[11]郑世超,霍梦琪,张燕玲,等.动态网络模块分析丹酚酸B治疗冠心病作用机制[J].中国科学:生命科学,2016,46(8):929.
[12] Li M,Li D,Tang Y,et al. CytoCluster:acytoscapeplugin for cluster analysis and visualization of biological networks[J]. Int J Mol Sci,2017,18(9):1880.
[13] Li M,Chen J,Wang J,et al. Modifying the DPClus algorithm for identifying protein complexes based on new topological structures[J]. BMC Bioinformatics,2008,9(1):398.
[14] Maere S,Heymans K,Kuiper M. BiNGO:a cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks[J]. Bioinformatics,2005,21(16):3448.
[15]戚爱棣. HPLC法测定姜黄、郁金、广西莪术中姜黄素的含量[J].中草药,2002,33(6):510.
[16] Kim D C,Ku S K,Bae J S. Anticoagulant activities of curcumin and its derivative[J]. BMB Rep,2012,45(4):221.
[17] Lievens D,Von H P. Platelets in atherosclerosis[J]. ThrombHaemost,2011,106(5):827.
[18]龚勇珍,孙少卫,廖端芳.细胞炎症反应与脂质代谢的相互作用及调节[J].中国动脉硬化杂志,2017,25(6):623.
[19] Kim Y W,Byzova T V. Oxidative stress in angiogenesis and vascular disease[J]. Blood,2014,123(5):625.
[20]季鹏,赵文明,于桐.柚皮素的最新研究进展[J].中国新药杂志,2015,24(12):1382.
[21]孟文婷,李东翔,佟玲.缺血性脑卒中的治疗研究进展[J].中国新药杂志,2016,25(10):1114.
[22]黄瑀莘,王柳萍,吴桂甫,等.莪术对局灶性脑缺血模型大鼠的神经保护作用[J].广西医科大学学报,2015,32(6):883.
[23] Cho W,Nam J W,Kang H J,et al. Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of i NOS,COX-2 and pro-inflammatory cytokines via the down regulation of NF-kappaB pathway in LPS-stimulated murine macrophages[J]. Int Immunopharmacol,2009,9(9):1049.
[24]何洁英,王汝上,何洁宝,等.郁金醇提取物对过氧化氢诱导的人脐静脉内皮细胞氧化应激损伤的保护作用[J].中国实验方剂学杂志,2013,19(3):223.
[25] Sasaki Y,Goto H,Tohda C,et al. Effects of curcuma drugs on vasomotion in isolated rat aorta[J]. Biol Pharm Bull,2003,26(8):1135.
[26]黎鹏程,程丑夫.论痰瘀是冠状动脉脂质斑块的主要病理基础[J].中医药导报,2012,18(7):5.
[27]邹永伟,邹华伟,牟春平.糖化血红蛋白异常与冠心病的相关性研究进展[J].中国老年学,2015,35(2):560.
[28]贝俊杰,孟璟.血小板微粒与心血管疾病[J].中国动脉硬化杂志,2013,21(9):849.
[29]马丽芬,苏振丽,王文科,等.姜黄素对2型糖尿病肾病模型大鼠肾脏氧化应激以及脂质代谢的保护作用[J].中国老年学杂志,2017,37(9):2128.
[30]王文祥,熊晓滨,毛卫红.姜黄素对高脂血症兔血液流变学、血小板聚集、抗氧化以及纤溶系统的影响[J].中国现代应用药学,2013,30(6):598.
[31]曾克武,屠鹏飞.固相亲合载体应用于中药复杂体系直接作用靶点研究的现状与挑战[J].中国中药杂志,2017,42(19):3645.
[32] Derry M M,Somasagara R,Raina K,et al. Target identification of grape seed extract in colorectal cancer using drug affinity responsive target stability(DARTS)technique:role of endoplasmic reticulum stress response proteins[J]. Curr Cancer Drug Targets,2014,14(4):323.