Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology

Jia-xiang YU; An-na WANG; Yi ZHENG; He GUO; Nan JIANG; Yu-feng YANG; Yan SHI

doi:10.13422/j.cnki.syfjx.20202015

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Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology

Pharmacology | 更新时间：2020-12-10

- Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 21, Pages: 118-128(2020)
- 作者机构：
  
  辽宁中医药大学，沈阳 110847
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20202015
  CLC： R285;R289;R22;R2-031
- Received：20 February 2020，
  
  Published Online：31 July 2020，
  
  Published：05 November 2020
- 稿件说明：
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于嘉祥,王安娜,郑一等.基于网络药理学的半夏-橘红药对治疗代谢综合征的作用机制探析[J].中国实验方剂学杂志,2020,26(21):118-128.

YU Jia-xiang,WANG An-na,ZHENG Yi,et al.Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(21):118-128.
于嘉祥,王安娜,郑一等.基于网络药理学的半夏-橘红药对治疗代谢综合征的作用机制探析[J].中国实验方剂学杂志,2020,26(21):118-128. DOI： 10.13422/j.cnki.syfjx.20202015.

YU Jia-xiang,WANG An-na,ZHENG Yi,et al.Mechanism of Pinelliae Rhizoma-Citri Exocarpium Rubrum in Treatment of Metabolic Syndrome Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(21):118-128. DOI： 10.13422/j.cnki.syfjx.20202015.

摘要

目的

通过网络药理学研究方法，研究二陈汤中君、臣药物半夏-橘红治疗代谢综合征的作用机制。

方法

通过中药系统药理学数据库与分析平台（TCMSP）数据库检索半夏、橘红2味中药的有效成分，并用毒药物动力学（ADME）参数进行筛选，运用网络药理学在线数据库（TCMID），BATMAN-TCM，SymMap，TCM-MESH数据库并结合相关文献检索结果对TCMSP所获得的有效成分进行补充。利用TCMSP靶点预测模型预测药物可能的作用靶点。检索TTD，DRUGBANK，DisGeNET，CTD，GeneCards，OMIM，PharmGkb，京都基因与基因组百科全书（KEGG），DiGSeE数据库，获取代谢综合征的疾病靶点，从GEO数据库下载并分析芯片GSE98895，筛选正常人和代谢综合征患者的差异基因，对代谢综合征的疾病靶点数据库进行补充。用Rstudio 3.6.2取得半夏、橘红药物靶点与代谢综合征疾病靶点的交集。将上述交集靶点导入Metascape数据库中，进行模块分析和整体GO生物过程，KEGG和Reactome通路分析。用cytohubba插件从交集靶点筛选出核心靶点，将核心基因导入BioGPS，Genecards数据库分析核心靶点的组织分布和亚细胞分布，用DisGeNET数据库对核心靶点进行蛋白归属。

结果

共筛选出半夏、橘红34个有效成分，120个作用靶点，经Rstudio3.6.2取交集后，共得出115个靶点。Metascape模块分析和整体分析的结果基本一致，主要涉及神经活动配体-受体相互作用，钙离子，环磷酸鸟苷-通过蛋白激酶G（cGMP-PKG），胆碱能突触，甲状腺激素，胰岛素等生物过程。cytohubba插件筛选出17个靶点，涉及VEGFA，NOS3等17个关键基因。核心靶点的组织分布和亚细胞分布主要为淋巴母细胞，CD33

_Myeloid细胞，杏仁体，松果体和细胞质基质，线粒体等。其主要的蛋白归属为信号分子、激酶、核酸。

结论

半夏-橘红药对治疗代谢综合征通过血液循环，神经活动配体-受体相互作用，cGMP-PKG，白细胞介素，钙离子相关作用等复杂的生物过程和通路，说明中药治疗疾病是通过多成分、多靶点、多生物过程、多通路等多种途径实现的（从核心基因的组织分布、亚细胞分布、蛋白归属信息也可证明），证明了中医整体观念的优越性；二陈汤及其类方适合用于治疗代谢综合征，也体现了中医“异病同治”这一法则不仅仅体现在理论层面上；网络药理学需要和实验验证相结合才能更有说服力。

Abstract

Objective

By the method of network pharmacology， the mechanism of Pinelliae Rhizoma and Citri Exocarpium Rubrum in the treatment of metabolic syndrome was explored.

Method

Effective components of Pinelliae Rhizoma and Citri Exocarpium Rubrum were retrieved by TCMSP database，and then selected by ADME parameters. TCMID，BATMAN-TCM，SymMap，TCM-MESH database were used to supplement effective components of TCMSP. TCMSP target prediction model was used to predict potential targets of drugs. DRUGBANK，DisGeNET，CTD，GeneCards，OMIM，PharmGkb，KEGG，DiGSeE databases were retrieved to obtain the targets of metabolic syndrome，and the chips were downloaded and analyzed through GEO database No.GSE98895 to screen out the differential genes of normal people and patients with metabolic syndrome，and supplement the target databases of metabolic syndrome. The intersections of Pinelliae Rhizoma-Citri Exocarpium Rubrum and metabolic syndrome disease targets were obtained by Rstudio 3.6.2. The above intersection targets were imported into the Metascape database for module analysis and overall GO（Biological Process），KEGG and Reactome pathway analysis. The core targets were selected from the intersection targets by using the cytohubba plug-in，the core genes were input into the database of BioGPS，Genecards to analyze the tissue distribution and subcellular distribution，and the core targets were assigned by using the database of DisGeNET.

Result

A total of 34 active components and 120 targets of Pinelliae Rhizoma and Citri Exocarpium Rubrum were screened out，and 115 targets were obtained after the intersection of Rstudio 3.6.2. The results of Metascape module analysis and whole analysis were mostly the same，mainly involving the biological processes， such as ligand receptor interaction，calcium ion，cGMP-PKG，cholinergic synapse，thyroid hormone，insulin. The cytohubba plug-in was used to screen out 17 targets，involving 17 key genes， such as VEGFA and NOS3. The tissue and subcellular distribution of the core targets mainly included lymphoblasts，CD33

_myeloid cells，amygdala，pineal and cytoplasmic matrix，mitochondria. The main proteins were signal molecules，kinases and nucleic acids.

Conclusion

Pinelliae Rhizoma and Citri Exocarpium Rubrum could treat metabolic syndrome through complex biological processes and pathways，such as blood circulation，ligand receptor interaction of nerve activity，cGMP-PKG，interleukin-related action，calcium ion. This indicates that traditional Chinese medicine（TCM） treated diseases through multi-component，multi-target，multi biological processes，multi-channel and other ways（which is also proved by the distribution of core genes in the tissue，subcellular and protein ascription information），indicating the superiority of the holism concept of TCM. Erchetang and its similar prescriptions are suitable for treating metabolic syndrome，which also indicates that the principle of "treating different diseases with the same therapy" of TCM is not only reflected at the theoretical level； and network pharmacology needs to be further proved in the combination with experimental verification.

关键词

Keywords

references

中国 2 型糖尿病防治指南（2017年版）［J］. 中国实用内科杂志， 2018 ， 38 （ 4 ）： 292 - 344 .

GOODMAN D W S ， HULLEY S B ， CLARK L T ， et al . NCEP expert panel on detection，evaluation，and treatment of high blood cholesterol in adults（adult treatment panel Ⅲ）.Third report of the national cholesterol education program （NCEP）expert panel on detection，evaluation，and treatment of high blood cholesterol in adults（adult treatment panel Ⅲ）.final report ［J］. Circulation ， 2002 ， 106 ： 3143 - 3421 .

ZIMMET P P ， ALBERTI K G M M ， RIOS S M . A new international diabetes federation（IDF）worldwide definition of the metabolic syndrome：the rationale and the results ［J］. Revista Espa de Cardiologia ， 2005 ， 58 （ 12 ）： 1371 - 1376 .

JUSTIN I . ODEGAARD，A C.The immune system as a sensor of the metabolic state ［J］. Immunity ， 2013 ， 38 （ 4 ）： 644 - 654 .

SAMUEL V T ， SHULMAN G I . The pathogenesis of insulin resistance：integrating signaling pathways and substrate flux ［J］. J Clin Invest ， 2016 ， 126 （ 1 ）： 12 - 22 .

SHARMA V ， M C NEILL J H . Parallel effects of beta-adrenoceptor block-ade on cardiac function and fatty acid oxidation in the diabeticheart：Confronting the maze ［J］. World J Cardio1 ， 2011 ， 3 （ 9 ）： 281 - 302 .

李威，景龙，邢斌，等 . 二陈汤类方用药规律探析［J］. 北京中医药大学学报， 2008 ， 31 （ 7 ）： 445 - 447 .

中医药创新发展规划纲要（ 2006 —2020年）（节选）［J］. 中国中西医结合杂志， 2007 ， 27 （ 5 ）： 471 .

王永华，杨凌 . 基于系统药理学的现代中药研究体系［J］. 世界中医药， 2013 ， 8 （ 7 ）： 801 - 808 .

陈娟 . 代谢综合征与慢性肾脏病的关系及相关肾脏病理分析［D］. 济南：山东大学， 2018 .

TOZAWA M ， ISEKI C ， TOKASHIKI K ， et al . Metabolic syndrome and risk of developing chronic kidney disease in Japanese adults ［J］. Hypertension Res ， 2007 ， 30 （ 10 ）： 937 - 943 .

RAMESH P G V . Metabolic syndrome and chronic kidney disease：Current status and future directions ［J］. World J Nephrol ， 2014 ， 3 （ 4 ）： 210 - 219 .

范骁辉，程翼宇，张伯礼．网络方剂学：方剂现代研究的新策略［J］. 中国中药杂志， 2015 ， 40 （ 1 ）： 1 - 6 .

WANG J Q ， CHENG J ， ZHANG C ， et al . Cardioprotection effects of sevoflurane by regulating the pathway of neuroactive ligand-receptor interaction in patients undergoing coronary artery bypass graft surgery ［J］. Comput Mathemat Methods Med ， 2017 ， 2017 ： 1 - 7 .

KONG Y ， LIANG X ， LIU L ， et al . High throughput sequencing identifies microRNAs mediating α-synuclein toxicity by targeting neuroactive-ligand receptor interaction pathway in early stage of drosophila Parkinson's disease model ［J］. PLoS One ， 2015 ， 10 （ 9 ）： e0137432 .

PALMI M ， MEINI A . Role of the nitric oxide/cyclic GMP/Ca 2+ signaling pathway in the pyrogenic effect of interleukin-lbeta ［J］. Mol Neurobiol ， 2002 ， 25 （ 2 ）： 133 - 147 .

VANDAEL DH ， MAHAPATRA S ， CALORIO C ， et al . Cav1.3 and Cav1.2 channels of adrenal chromaffin cells： emerging views on cAMP/cGMP-mediated phosphorylation and role in pacemaking ［J］. Biochim Biophys Acta ， 2013 ， 1828 （ 7 ）： 1608 - 1618 .

蔡婧 . 甲状腺功能与代谢综合征及甲功相关基因多态性的关联性研究［D］. 西安：第四军医大学， 2016 .

TISCHER E ， MITCHELL R ， HARTMAN T ， et al . The human gene for vascular endothelial growth factor.multiple protein forms are encoded through alternative exon splicing ［J］. Biol Chem ， 1991 ， 266 （ 18 ）： 11947 - 11954 .

CARMELIET P ， FERREIRA V ， BREIER G ， et al . Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele ［J］. Nature ， 1996 ， 380 （ 6573 ）： 435 - 439 .

BRESSLER J ， PANKOW J S ， CORESH J ， et al . Interaction between the NOS3 gene and obesity as a determinant of risk of type 2 diabetes：the atherosclerosis risk in communities study ［J］. PLoS One ， 2013 ， 8 （ 11 ）： e79466 .

CLAPAUCH R ， ANDRÉ F M ， MECENAS A S ， et al . Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors：importance of ESR1 and NOS3 polymorphisms ［J］. PLoS One ， 2014 ， 9 （ 7 ）： e103444 .

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