基于整合药理学平台探究半夏白术天麻汤治疗高血压的分子机制

徐男; 王亮; 时海燕; 李晓宇; 张成博; 孙蓉

doi:10.13422/j.cnki.syfjx.20182013

您当前的位置：

首页 >

文章列表页 >

基于整合药理学平台探究半夏白术天麻汤治疗高血压的分子机制

药理 | 更新时间：2021-02-09

- 基于整合药理学平台探究半夏白术天麻汤治疗高血压的分子机制
- Molecular Mechanism of Banxia Baizhu Tianma Tang in Treating Hypertension Based on Integrated Pharmacological Platform
- 中国实验方剂学杂志 2019年25卷第2期页码：109-117
- 作者机构：
  
  1.山东省中医药研究院，济南　 250014；
  2.山东中医药大学　中医学博士后流动站，济南　 250355；
  3.山东省千佛山医院，济南　 250014；
  4.山东大学　高等医学研究院，济南　 250012
- 作者简介：
  
  徐男，博士，助理研究员，从事中药新药开发与药效物质研究，E-mail：93679706@qq.com
  *孙蓉，教授，博士生导师，从事中药药理与毒理学研究，E-mail：sunrong107@163.com
- 基金信息：
  
  山东省中医药科技发展计划项目(2017-136);山东省重点研发计划项目(2017CXGC1308);山东省泰山学者工程专项(ts201511107)
- DOI：10.13422/j.cnki.syfjx.20182013
  中图分类号： R22; R24; R28; C37; R544.1
- 收稿日期：2018-01-15，
  
  网络出版日期：2018-08-02，
  
  纸质出版日期：2019-01-20
- 稿件说明：
移动端阅览
徐男, 王亮, 时海燕, 等. 基于整合药理学平台探究半夏白术天麻汤治疗高血压的分子机制[J]. 中国实验方剂学杂志, 2019,25(2):109-117.

Nan XU, Liang WANG, Hai-yan SHI, et al. Molecular Mechanism of Banxia Baizhu Tianma Tang in Treating Hypertension Based on Integrated Pharmacological Platform[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 109-117.
徐男, 王亮, 时海燕, 等. 基于整合药理学平台探究半夏白术天麻汤治疗高血压的分子机制[J]. 中国实验方剂学杂志, 2019,25(2):109-117. DOI： 10.13422/j.cnki.syfjx.20182013.

Nan XU, Liang WANG, Hai-yan SHI, et al. Molecular Mechanism of Banxia Baizhu Tianma Tang in Treating Hypertension Based on Integrated Pharmacological Platform[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(2): 109-117. DOI： 10.13422/j.cnki.syfjx.20182013.

摘要

目的：

探讨半夏白术天麻汤治疗高血压的分子机制。

方法：

综合利用中药整合药理学平台(TCM-IP)的中药方剂数据库、中药材数据库、中药成分数据库和疾病/症状靶标数据库的信息和分析功能，检索方中中药所含的化学成分信息，构建半夏白术天麻汤作用的潜在靶标和疾病靶标之间的相互作用网络，然后富集计算核心靶标，进行基因功能分析和通路分析，再进一步构建“中药材-化学成分-核心靶标-关键通路”多维关系网络。

结果：

对半夏白术天麻汤预测共得到90个活性成分，包括生物碱、核苷、黄酮、皂苷、有机酸等；涉及287个核心靶标，其中包括13个直接靶标，如腺苷酸环化酶，G蛋白偶联

受体，葡萄糖激酶等；涉及神经系统、内分泌系统、循环系统、雌激素信号通路、趋化因子信号通路、促性腺激素释放激素信号通路等相关生物过程和信号通路。

结论：

半夏白术天麻汤通过调节神经递质浓度和活性异常、改善胰岛素抵抗、调节炎症因子的产生、抑制炎症反应等过程来发挥保护血管内皮细胞的药理作用，进而达到治疗高血压的临床疗效，为全面阐释该方的作用机制提供了参考。

Abstract

Objective:

To explore the molecular mechanism of Banxia Baizhu Tianma Tang in treating hypertension.

Method:

Based on an internet-based computation platform for integrated pharmacology of traditional Chinese medicine(TCM)

TCM prescription database

TCM database

TCM component database and disease/symptoms target database

information on the chemical compositions contained in TCM was retrieved

an interaction network between potential targets and disease targets of Banxia Baizhu Tianma Tang was built

then core target was enriched and calculated

gene function and pathway analysis was carried out

the multi-dimensional relationship network of "Chinese herbs-ingredients-critical targets-key pathways" of Banxia Baizhu Tianma Tang was further constructed.

Result:

A total of 90 active ingredients in Banxia Baizhu Tianma Tang were obtained

including alkaloids

nucleosides

flavonoids

saponins

organic acids and other ingredients; they involved 287 core targets

including 13 direct targets

such as adenylate cyclase

G protein coupled with

receptor

glucose kinase

etc; they also involved nervous system

endocrine system

circulatory system

estrogen signaling pathway

chemokine signaling pathway and other related biological processes and signaling pathways.

Conclusion:

Banxia Baizhu Tianma Tang can regulate neurotransmitter concentration and activity abnormalities

improve the protective effect of vascular endothelial cells by improving insulin resistance

regulating the production of inflammatory factors

and inhibiting inflammatory reactions

thereby exerting pharmacological effects on the treatment of hypertension.This study can provide a scientific basis for comprehensive interpretation of mechanism of Banxia Baizhu Tianma Tang.

关键词

Keywords

references

张伯礼，王永炎．方剂关键科学问题的基础研究——以组分配伍研制现代中药 [J]. 中国天然药物， 2005 , 3 ( 5 ): 258 - 261 .

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 .

韦明婵，林江，莫明月，等．网络方剂学特征的研究进展 [J]. 中国实验方剂学杂志， 2016 , 22 ( 11 ): 218 - 224 .

吴纯伟，路丽，梁生旺，等．药物靶标预测技术在中药网络药理学中的应用 [J]. 中国中药杂志， 2016 , 41 ( 3 ): 377 - 382 .

HU P Y , YUE P F , ZHENG Q , et al . Pharmacokinetic comparative study of gastrodin after oral administration of Gastrodia elata Bl. extract and its compatibility with the different indigents of Ligusticum chuanxiong Hort. to rats [J]. J Ethnopharmacol , 2016 , 191 : 82 - 86 .

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 .

徐男．半夏白术天麻汤半仿生-酶法提取工艺的药材组合 [J]. 中国实验方剂学杂志， 2015 , 21 ( 13 ): 16 - 19 .

YANG Y , WANG X , ZHAO C , et al . Chemical mapping of essential oils，flavonoids and carotenoids in citrus peels by Raman microscopy [J]. J Food Sci , 2017 , 82 ( 12 ): 2840 - 2846 .

王淑玲，孙秀梅，张兆旺，等．半夏白术天麻汤4种提取液对高血压痰湿壅盛型大鼠的影响 [J]. 中国实验方剂学杂志， 2010 , 16 ( 18 ): 179 - 182 .

王淑玲，徐男，孙云廷，等．截留相对分子质量≤1000半夏白术天麻汤4种提取液对原发性高血压大鼠血清中单胺类递质的影响 [J]. 药物评价研究， 2016 , 39 ( 5 ): 772 - 777 .

王淑玲，徐男，孙剑峰，等．半夏白术天麻汤4种方法≤1000Da小分子混合物对高血压大鼠血管紧张素Ⅱ、一氧化氮和内皮素含量的影响 [J]. 健康研究， 2017 , 37 ( 5 ): 510 - 513 .

许海玉，刘振明，付岩，等．中药整合药理学计算平台的开发与应用 [J]. 中国中药杂志， 2017 , 42 ( 18 ): 3633 - 3638 .

邓冬，王伟，李雪丽，等．中药复方治疗高血压机制的研究进展 [J]. 中草药， 2017 , 48 ( 21 ): 4565 - 4570 .

Chee M J , Pissios P , Maratos-Flier E. Neurochemical characterization of neurons expressing melanin-concentrating hormone receptor 1 in the mouse hypothalamus [J]. J Comp Neurol , 2013 , 521 ( 10 ): 2208 - 2234 .

Sanabra C , Mengod G. Neuroanatomical distribution and neurochemical characterization of cells expressing adenylyl cyclase isoforms in mouse and rat brain [J]. J Chem Neuroanat , 2011 , 41 ( 1 ): 43 - 54 .

Da Silva M S , Chartrand D , Vohl M C , et al . Dairy product consumption interacts with glucokinase(GCK) gene polymorphisms associated with insulin resistance [J]. J Pers Med , 2017 , doi: 10.3390/jpm7030008 10.3390/jpm7030008 .

Stella J , Buers I , van de Wetering K , et al . Effects of different variants in the ENPP1 gene on the functional properties of ectonucleotide pyrophosphatase/phosphodiesterase family member 1 [J]. Hum Mutat , 2016 , 37 ( 11 ): 1190 - 1201 .

Kobayashi M , Kawakami K. Synergism of the ATF/CRE site and GC box in the housekeeping Na，K-ATPase alpha1 subunit gene is essential for constitutive expression [J]. Biochem Biophys Res Commun , 1997 , 241 ( 1 ): 169 - 174 .

Isenovic E R , MENG Y , Jamali N , et al . Ang Ⅱ attenuates IGF-1-stimulated Na ＋，K ＋ -ATPase activity via PI3K/Akt pathway in vascular smooth muscle cells [J]. Int J Mol Med , 2004 , 13 ( 6 ): 915 - 922 .

Rajamanickam G D , Kastelic J P , Thundathil J C. The ubiquitous isoform of Na/K-ATPase (ATP1A1)regulates junctional proteins，connexin 43 and claudin 11 via Src-EGFR-ERK1/2-CREB pathway in rat Sertoli cells [J]. Biol Reprod , 2017 , 96 ( 2 ): 456 - 468 .

Lee M Y , Gamez-Mendez A , ZHANG J , et al . Endothelial cell autonomous role of Akt1：regulation of vascular tone and ischemia-induced arteriogenesis [J]. Arterioscler Thromb Vasc Biol , 2018 , 38 ( 4 ): 870 - 879 .

吴赛，姜月华，杨传华，等．半夏白术天麻汤对痰湿壅盛型高血压大鼠心肌MAPK信号通路的影响 [J]. 中国实验方剂学杂志， 2016 , 22 ( 8 ): 159 - 165 .

姜凌宇，姜月华，杨传华，等．半夏白术天麻汤对痰湿壅盛型高血压模型大鼠下丘脑蛋白质组学的影响 [J]. 中医杂志， 2017 , 58 ( 13 ): 1139 - 1144 .

Maneesai P , Bunbupha S , Kukongviriyapan U , et al . Effect of asiatic acid on the Ang Ⅱ-AT 1 R-NADPH oxidase-NF- κ B pathway in renovascular hypertensive rats [J]. Naunyn Schmiedebergs Arch Pharmacol , 2017 , 390 ( 10 ): 1073 - 1083 .

WU Q , CHEN J X , CHEN Y , et al . The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation [J]. Cell Death Dis , 2018 , doi: 10.1038/s41419-018-0267-9 10.1038/s41419-018-0267-9 .

ZHAI Y K , GUO X Y , GE B F , et al . Icariin stimulates the osteogenic differentiation of rat bone marrow stromal cells via activating the PI3K-AKT-eNOS-NO-cGMP-PKG [J]. Bone , 2014 , 66 : 189 - 198 .

Vargas-Martínez F , Schanler R J , Abrams S A , et al . Oxytocin，a main breastfeeding hormone，prevents hypertension acquired in utero：a therapeutics preview [J]. Biochim Biophys Acta , 2017 , 1861 ( 1 Pt A ): 3071 - 3084 .

LIU S , PAN S , TAN J , et al . Oxytocin inhibits ox-LDL-induced adhesion of monocytic THP-1 cells to human brain microvascular endothelial cells [J]. Toxicol Appl Pharmacol , 2017 , 337 : 104 - 110 .

Knauf C , Chuo? M M , Jirou-Najou J L , et al . Involvement of NPY Y2 receptor subtype in the control of the spontaneous NO/GnRH release at the rat median eminence [J]. Neuroreport , 2001 , 12 ( 15 ): 3365 - 3369 .

CHEN S , HAO X , YU L , et al . Gastrodin causes vasodilation by activating KATP channels in vascular smooth muscles via PKA-dependent signaling pathway [J]. J Recept Signal Transduct Res , 2017 , 37 ( 6 ): 543 - 549 .

Giménez-Bastida J A , González-Sarrías A , Vallejo F , et al . Hesperetin and its sulfate and glucuronide metabolites inhibit TNF- α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1(PAI-1)levels [J]. Food Funct , 2016 , 7 ( 1 ): 118 - 126 .

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 .

庄耀东，王永发，陈晓红，等．代谢综合征痰证与胰岛素抵抗指数、血脂及BMI的相关性研究 [J]. 中医药临床杂志， 2016 , 28 ( 11 ): 1600 - 1602 .

万晓华，陈小光，徐丹苹，等．高血压病中医痰证与客观化指标相关性研究概述 [J]. 现代中西医结合杂志， 2017 , 26 ( 14 ): 1590 - 1593 .

蔡少青，王璇，尚明英，等．中药“显效理论”或有助于阐释并弘扬中药特色优势 [J]. 中国中药杂志， 2015 , 40 ( 17 ): 3435 - 3443 .

徐风，杨东辉，尚明英，等．中药药效物质的“显效形式”、“叠加作用”和“毒性分散效应”——由中药体内代谢研究引发的思考 [J]. 世界科学技术—中医药现代化， 2014 , 16 ( 4 ): 688 - 703 .

刘钊，钟菊迎，高尔宁，等．解毒活血中药组分复方对脂多糖诱导巨噬细胞炎症反应的抑制作用 [J]. 中国实验方剂学杂志， 2017 , 23 ( 1 ): 25 - 29 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

丹参及有效成分的抗抑郁药理作用及机制的研究进展

基于LC/Q-TOF-MS整合网络药理学探讨潜阳育阴颗粒防治高血压肾损害的药效物质基础与作用机制

基于整合药理学平台探究三棱抗血栓形成及抗血小板聚集的分子机制

基于整合药理学分析丁香柿蒂汤降逆止呃的分子机制