* 张燕玲黄明峰王元明高静乔延江 ** / 100102 本文利用中药有效成分族辨识技术, 针对血府逐瘀汤中 668 个化学成分进行了活性辨 识, 命中化合物达到 213 个 命中靶标为 20 个采用 Cytoscape 软件建立药物 - 靶点相互作用网络模 型, 并探讨其多成分 - 多靶点 - 多疾病相关关系研究结果表明, 血府逐瘀汤活性成分可调控 ACE AngII TNFα COX 2 5-LOX 等靶点, 涉及炎症和心血管受体, 与高血压 心绞痛等多种疾病相关, 揭示 血府逐瘀汤治疗冠心病可能的作用机理, 并提示其可能具有新功效的研究前景 : 有效成分族辨识血府逐瘀汤方剂配伍 doi: 10.3969/j.issn.1674-3849.2012.04.008 [2] [1] * ** 收稿日期 :2012-07-09 修回日期 :2012-08-13 科学技术部国家科技支撑计划项目 (2008BAI51B01): 中药有效成分族辨识研究, 负责人 : 张宏桂 ; 国家自然基金项目 (81173522): 点线面 三维模拟活血化瘀中药防治冠心病的作用机制研究, 负责人 : 张燕玲 ; 北京中医药大学自主课题 (2011-JDJS-12): 活血化瘀中药治疗冠心 病的作用机制研究, 负责人 : 张燕玲 ; 科学技术部国家 重大新药创制 科技重大专项 (201ZX09401-028): 基于源头创新的中药孵化基地建 设, 负责人 : 刘安 通讯作者 : 乔延江, 本刊编委, 教授, 博士生导师, 北京中医药大学副校长, 主要研究方向 : 中药信息工程, 中药质量控制,Tel:010-84738620, E-mail:yjqiao@263.net 1793
1. 血府逐瘀汤化学成分集 1 668-2 COX-2 Cyclooxyenase-2 99 Corticotropin-releading [3] 65 hormone, CRH HDAC [4] 92 2 Cyclin-dependent Kinase, CDK2 /CyclinA Glutamate, [5~7] 15 GLU (Tumor necrosis factorα, TNFα) γ- Gamma-amino [8,9] 46 butyric acid GABA receptor [10,11] anthrax lethal factor, LF 26 ACE Angiotensin-1 Converting Enzyme P38 P38 mitogen - [12] 30 activated protein kinase inhibitors, p38mapk [13~15] α 190 Noncompetitive AMPA receptor [16,17] 60 II Angiotensin II, AngII AT1 human epidermalgrowth [18,19] 15 factor receptor -2, HER2 5 -HT2A 5 - A hydroxytryptamine 2A PAF Platelet - [20,21] activating factor 5-5 - 30 lipoxygenase, 5 -LOX integrase inhibitor, IN [22,23] neuraminidase, NA -1β Interlenkin -1β converting enzyme, ICE 2. 血府逐瘀汤有效成分辨识 58 [24,25] PAF [26] [27] TNF [28] Cytoscape - 32 1 12 1 14 112 4 2 1 Raf-1 Raf-1 kinase 2. 血府逐瘀汤药物 - 靶点相互作用网络 1 1. 血府逐瘀汤有效成分辨识结果 213 21 13 1794
1 药味柴胡当归地黄赤芍红花桃仁枳壳甘草 命中药效团辨识模型 CDK2/CyclinA COX 2 GABA HDAC LF P38MAPK Raf-1kinase TNF ACE AMPA CDK2/CyclinA COX 2 CRH GLU Raf-1kinase CDK2/CyclinA COX 2 CRH GABA GLU HDAC ICE LF P38MAPK Raf-1kinase COX 2 GABA 5-HT 2A AngII CDK2/CyclinA COX 2 PAF Raf-1kinase IN NA P38MAPK P38MAPK COX 2 CRH HDAC TNF 5-HT 2A 5-LOX ACE AMPA AngII CDK2/CyclinA COX 2 CRH GLU HDAC HER2 IN NA PAF Raf-1kinase TNF 川芎 ACE COX 2 牛膝 桔梗 COX 2 CRH AngII 1795
1 分子层面解释血府逐瘀汤治疗高血压 - - I II AngII AngII AngII 2 分子层面解释血府逐瘀汤治疗心绞痛 COX 2 5-LOX PAF TNF-α 1.. -, 2008, 10(5) 94~97. 3 分子层面解释血府逐瘀汤保护心肌缺血 p38mapk, 2006, 19(3) 216~218. 4 p38mapk 2006, 28(4) 609~611. p38mapk 2005, 20(121) 79~83. 7,,, 2003, 5(19) 21~23.., 2003, 19(9) 965~970. HDAC CDK2/CyclinA 27(1) 67~69. 10, 2,,,.., 2004, 5(8) 111~112. 3,...., 2005, 2 (23) 120. 5,,.., 6,,..,,.. 8,,,. 9,,,.., 2008,.., 2006, 17(9) 1666~1667. 11,.., 2007, 13(5) 65~69. 12,,,.., 2007, 18(24) 1903~1904. 13.. 14,,. (11) 1~4. 15,, 2008, 31(12) 1812~1815. 16,,, 1995, 5 31~35., 2001, 24(3) 222~224.., 2006, 8,..,.. 1796
17,,.. 23.., 2006, 37(1) 115~119., 2007, 18(2) 506~509. 18,,.. 24,,,., 2006, 17(7) 1298~1299. 19,,.., 25, 2009, 1 101~102. 20,.. 26,, 1998, 18(12) 756~758. 21.., 2009, 27 21(3) 66~67. 20(1) 50~52. 22,.., 2007, 20(5) 443~446.., 2000, 35(11) 741.,,.., 2001, 23(4) 21.,,.., 2000, 20(5) 44..., 1994, 28.., 2010, 21(2) 362~364. Identification of Active Compounds and Potential Targets of Xue-Fu-Zhu-Yu-Tang Zhang Yanling, Huang Mingfeng, Wang Yuanming, Gao Jing, Qiao Yanjiang (Research Center of Traditional Chinese Medicine Information Engineering / Beijing Key Laboratory of Chinese Pharmaceuticals and Drug Innovation, Beijing University of Chinese Medicine, Beijing 100102, China) Abstract: Identification Technology of Active Clusters (ITAC) was used to reveal the compatibility of Xue-Fu- Zhu-Yu-Tang (XFZY). All 668 compounds were found from XFZY, and 58 pharmacophores were used to identify active compounds. All 213 compounds and 20 targets were identified. Most of the function of the targets related to cardiovascular disease, inflammation and cancer. Compound-target interaction network was constructed by Cytoscape. Then, the mechanism of the multi-compounds act on multi-targets was analyzed to reveal the mechanism of prevention and treatment on coronary heart disease by XFZY. New potential indications of XFZY were also suggested by this paper. Keywords: Identification Technology of Active Clusters (ITAC), Xue-Fu-Zhu-Yu-Tang, prescription compatibility ( 责任编辑 : 李沙沙张志华, 责任译审 : 王晶 ) 1797