Pharmacological Mechanism of Xiao Xianxiongtang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology

Lan-er SHI; Ke-chao NIE; Wen-jing ZHANG; Mei-si ZHENG; Chuang LIU; Zhang-zhi ZHU

doi:10.13422/j.cnki.syfjx.20200105

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Pharmacological Mechanism of Xiao Xianxiongtang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology

Data Mining | 更新时间：2021-02-09

- Pharmacological Mechanism of Xiao Xianxiongtang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 4, Pages: 198-206(2020)
- 作者机构：
  
  1.广州中医药大学　第一临床医学院，广州　 510405
  2.广州中医药大学　第一附属医院，广州　 510405
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20200105
  CLC： R2-0; R22; R285.5; R289
- Received：24 June 2019，
  
  Published Online：11 September 2019，
  
  Published：20 February 2020
- 稿件说明：
移动端阅览
Lan-er SHI, Ke-chao NIE, Wen-jing ZHANG, et al. Pharmacological Mechanism of Xiao Xianxiongtang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 198-206.
DOI：

Lan-er SHI, Ke-chao NIE, Wen-jing ZHANG, et al. Pharmacological Mechanism of Xiao Xianxiongtang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(4): 198-206. DOI： 10.13422/j.cnki.syfjx.20200105.

摘要

目的：

利用网络药理学探索小陷胸汤治疗2型糖尿病(T2DM)的药理机制。

方法：

在中药系统药理学技术平台(TCMSP)网站检索小陷胸汤的主要活性成分、对应的作用靶点及靶标基因，通过人类基因数据库(Gene Cards)获得T2DM的相关靶标基因，将药物活性成分靶点与T2DM靶点相映射，获得交集靶点即为小陷胸汤作用于T2DM的预测靶点。利用Cytoscape 3.7.1软件构建药物活性成分-交集靶点网络模型，选出关键活性成分。利用STRING网站构建交集靶点蛋白相互作用网络(PPI)，选出关键靶点基因。利用DAVID 6.8在线工具对交集靶点进行基因本体(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。

结果：

小陷胸汤作用于T2DM的活性成分有30个，相关靶点156个，关键有效成分14个，关键靶点基因18个。GO分析显示，小陷胸汤治疗T2DM潜在基因的生物功能主要涉及转录调控、氧化应激、蛋白结合和炎症反应等；KEGG通路富集显示小陷胸汤治疗T2DM影响的通路主要有缺诱导因子-1(HIF-1)信号通路，肿瘤坏死因子(TNF)信号通路，Toll样受体信号通路，甲状腺激素信号通路，磷脂酰肌醇氧3激酶/蛋白激酶B(PI3K/Akt)信号通路，乙肝，丙肝，酪氨酸激酶受体2(ErbB)信号通路，钙离子信号通路和核转录因子-

B(NF-кB)信号通路等。

结论：

小陷胸汤治疗T2DM机制可能是通过抑制炎症因子分泌，参与抗炎反应，降低氧化应激，升高细胞内钙离子浓度，阻断胰高血糖素信号通路，激活PI3K/Akt通路等来改善胰岛素抵抗，提高胰岛素敏感性，降低血糖。

Abstract

Objective:

To explore the pharmacological mechanism of Xiao Xianxiongtang in treating type 2 diabetes mellitus (T2DM) by network pharmacology.

Method:

The main active ingredients

corresponding targets and target genes of Xiao Xianxiongtang were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) website. Relevant target genes of T2DM were obtained through Gene Cards. The targets of drug active ingredients were mapped to the targets of T2DM

and the intersection targets were obtained as the predictive targets of Xiao Xianxiongtang on T2DM. Cytoscape 3.7.1 software was used to construct the drug active ingredient-intersection target network model and select the key active ingredients. Interactive protein-protein interaction network (PPI) was constructed by STRING website

and key target genes were selected. Gene function analysis (GO) and enrichment analysis based on the Kyoto encyclopedia of genes and genomes (KEGG) pathway were performed on the intersecting targets using DAVID6.8 online tool.

Result:

Xiao Xianxiongtang had 30 active ingredients

156 relevant targets

14 key active ingredients and 18 key target genes on T2DM. GO analysis showed that the biological functions of Xiao Xianxiongtang in the treatment of potential genes of T2DM mainly involved transcriptional regulation

oxidative stress

protein binding and inflammatory reaction. KEGG pathway enrichment showed that the main pathways of Xiao Xianxiongtang in the treatment of T2DM were hypoxia inducible factor-1 (HIF-1) signaling pathway

tumor necrosis factor (TNF) signaling pathway

Toll-like receptor signaling pathway and thyroid hormone signaling pathway

phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway

hepatitis B

hepatitis C

tyrosine kinase receptor2(ErbB) signaling pathway

calcium signaling pathway and nuclear factor-kappa B (NF-

B) signaling pathway.

Conclusion:

Xiao Xianxiongtang is a multi-component

multi-target and multi-pathway process in the treatment of T2DM. It plays an important role in the treatment of T2DM by regulating transcription

oxidative stress

protein binding and inflammatory reaction.

Conclusion:

The mechanism of Xiao Xianxiongtang in treating T2DM may alleviate insulin resistance

increase insulin sensitivity and reduce blood sugar by inhibiting the secretion of inflammatory factors

participating in anti-inflammatory response

reducing oxidative stress

increasing intracellular calcium concentration

blocking glucagon signaling pathway and activating PI3K/Akt pathway.

关键词

Keywords

references

G QI , C LIANG , C Keping ． Treatment of diabetes mellitus using iPS cells and spice polyphenols [J]． J Diabetes Res ， 2017 , doi： 10.1155/2017/5837804 http://dx.doi.org/10.1155/2017/5837804 .

X SHEN ， A Vaidya ， S WU ， et al . The diabetes epidemic in china: an integrated review of national surveys [J]. Endocr Pract ， 2016 ， 22 : 1119 - 1129 .

World Health Organization . Definition, diagnosis and classification of diabetes mellitus and its complications. part 1: Diagnosis and classification of diabetes mellitus [M]. Geneva ： Department of Noncommunicable Disease Surveillance , 1999 .

施岚尔，聂课朝，张文婧，等．基于网络药理学探讨大黄黄连泻心汤治疗2型糖尿病作用机制 [J]．中国实验方剂学杂志， 2019 ， 25 ( 18 )： 160 - 166 .

宋丽娜，宋菊敏．胰岛 β 细胞胰岛素抵抗的研究进展 [J]．医学综述， 2009 ， 15 ( 3 )： 440 - 442 .

张利民，邹莲霞，巫祖强，等．小陷胸汤对糖尿病前期痰湿蕴热质患者胰岛素抵抗指数及 β 细胞功能的影响 [J]．成都中医药大学学报， 2018 ， 41 ( 4 )： 52 - 55 .

张增建．加味小陷胸汤治疗糖尿病皮肤瘙痒症疗效观察 [J]．光明中医， 2016 ， 31 ( 3 )： 361 - 362 .

陈凯，刘馨，管怡晴，等．基于网络药理学构建新型中药复方降压抗纤方抗高血压心肌纤维化的作用 [J]．中国实验方剂学杂志， 2018 ， 24 ( 20 )： 115 - 122 .

师帅，胡元会，吴华芹，等． “丹参-三七”药对作用机制的网络药理学探讨 [J]．中国实验方剂学杂志， 2018 ， 24 ( 18 )： 192 - 197 .

王萍，唐仕欢，苏瑾，等．基于整合药理学的中药现代研究进展 [J]．中国中药杂志， 2018 ， 43 ( 7 )： 1297 - 1302 .

J RU , P LI , J WANG , et al . TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform , 2014 ， 6 ( 1 )： 13 .

Y F YANG , L YAN , J H WANG , et al . Systematic investigation of Ginkgo biloba leaves for treating cardio-cerebrovascular diseases in an animal model [J]. ACS Chem Biol , 2017 , 12 ( 5 )： 1363 - 1372 .

卢文丹，李莉，申艳佳，等．基于血管舒缩相关GPCR靶点的小续命汤网络药理学研究 [J]．中国中药杂志， 2018 ， 43 ( 23 )： 4698 - 4708 .

S K Panchal ， H Poudyal ， L Brown . Quercetin ameliorates cardiovascular，hepatic, and metabolic changes in diet-induced metabolic syndrome in rats [J]. J Nutr , 2012 ， 142 ( 6 )： 1026 - 1032 .

R Dhanya , A D Arya , P Nisha , et al . Quercetin，a lead compound against type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line [J]. Front Pharmacol , 2017 , 8 ： 336 .

H J Kwak , D YANG , Y Hwang , et al . Baicalein protects rat insulinoma INS-1 cells from palmitate-induced lipotoxicity by inducing HO-1 [J]. PLoS One , 2017 , 12 ( 4 )： e0176432 .

J R YANG , J G LUO , L Y KONG . Determination of α -glucosidase inhibitors from Scutellaria baicalensis using liquid chromatography with quadrupole time of flight tandem mass spectrometry coupled with centrifugal ultrafiltration [J]． Chin J Nat Med ， 2015 ， 13 ( 3 )： 208 - 214 .

M CHEN , Z D YANG , K M Smith , et al . Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity [J]. Diabetologia , 2005 , 48 ( 3 )： 486 - 495 .

Y FU ， J LUO ， Z JIA ， et al . Baicalein protects against type 2 diabetes via promoting islet β -cell function in obese diabetic mice [J]. Int J Endocrinol , 2014 ， doi： 10.1155/2014/846742 http://dx.doi.org/10.1155/2014/846742 .

J J Jeong , S E JANG , S R Hyam , et al . The rhizome mixture of anemarrhena asphodeloides and coptidis chinensis ameliorates acute and chronic colitis mice by inhibiting the binding of lipopolysaccharide to TLR4 and IRAK1 phosphorylation [J]. Evid Based Complement Alternat Med , 2014 ， 10 ： 1 - 11 .

李爱云，杨京，张昕宇，等．小檗碱治疗2型糖尿病降血糖机制的研究进展 [J]．中国实验方剂学杂志， 2019 ， 25 ( 22 )： 219 - 226 .

邓舒妮，张学思，李新玥，等．慢性丙型肝炎病毒感染患者发生2型糖尿病的流行病学调查 [J]．中华医院感染学杂志， 2016 ， 26 ( 6 )： 1279 - 1283 .

张蕙彦．慢性乙型肝炎病人2型糖尿病流行情况调查与相关因素分析 [J]．中国卫生产业， 2014 ， 11 ( 33 )： 56 - 57 .

李平，汪茂荣．丙型肝炎病毒感染与2型糖尿病相关性研究进展 [J]．实用肝脏病杂志， 2016 ， 19 ( 2 )： 253 - 256 .

C M Girgis , K CHENG , C H Scott , et al . Novel links between HIFs, type 2 diabetes, and metabolic syndrome [J]. Trends Endocrinol Metab , 2012 , 23 ( 8 )： 372 - 380 .

M H XIA , R I HUANG , G L Semenza , et al . Identification of chemical compounds that induce HIF-1a activity [J]． Toxicol Sci , 2012 , 112 ( 1 )： 153 - 163 .

M Croft , C A Benedict , C F Ware . Clinical targeting of the TNF and TNFR superfamilies [J]. Nat Rev Drug Discov , 2013 ， 12 ( 2 )： 147 - 168 .

M F Hivert ， L M Sullivan ， C S Fox ， et al . Associations of adiponectin，resistin，and tumor necrosis factor-alpha with insulin resistance [J]. J Clin Endocrinol Metab ， 2008 ， 93 ( 8 )： 3165 - 3172 .

A Gratas-Delamarche , F Derbré , S Vincent , et al . Physical inactivity, insulin resistance, and the oxidative-inflammatory loop [J]. Free Radic Res ， 2014 ， 48 ( 1 )： 93 - 108 .

危正南，李涛，张庆红，等． MIF、TLR4、TNF- α 水平在糖尿病肾病患者中的变化及其临床意义 [J]．疑难病杂志， 2016 ， 15 ( 2 )： 165 - 168 .

M Monden , H Koyama , Y Otsuka , et al . Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2 [J]. Diabetes , 2012 , 62 ( 2 )： 478 - 489 .

H S Kim ， M S HAN ， K W Chung ， et al . Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes [J]. Immunity , 2007 ， 27 ( 2 )： 321 - 333 .

F T Schulthess , F Paroni , N S Sauter , et al . CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling [J]. Cell Metab ， 2009 ， 9 ( 2 )： 125 - 139 .

刁红杰，鲁燕． Toll样受体4介导的炎症反应与肥胖和胰岛素抵抗的研究进展 [J]．中国糖尿病杂志， 2016 ， 11 ： 1044 - 1048 .

J J Kim , D D Sears . TLR4 and insulin resistance [J]. Gastroenterol Res Pract ， 2010 ， 10 ： 212563 .

马艳庆，张晓娟．甲状腺激素水平与2型糖尿病患者代谢指标的关联性研究 [J]．医药论坛杂志， 2018 ， 39 ( 12 )： 173 - 175 .

吴小梅，何爱琴，鲁一兵．糖尿病肾病患者甲状腺激素水平变化及其与肾功能的关系 [J]．山东医药， 2015 ， 55 ( 37 )： 37 - 39 .

贾方，王小娟，田晶，等 . 2型糖尿病患者中亚临床甲状腺功能减退症与慢性肾脏病的相关性分析 [J]．山西医科大学学报， 2014 ， 45 ( 11 )： 1028 - 1031 .

李斌，范源，李鑫．基于PI3K/Akt信号通路的中药治疗2型糖尿病胰岛素抵抗研究进展 [J]．中成药， 2017 ， 39 ( 1 )： 151 - 154 .

K Lemmens , K Doggen , G W De Keulenaer . Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure [J]. Circulation ， 2007 , 116 ( 8 )： 954 - 960 .

X LIU , X GU , Z LI , et al . Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy [J]. J Am Coll Cardiol , 2006 , 48 ( 7 )： 1438 - 1447 .

雷蕾，桂春，胡明，等 . ErbB2受体在糖尿病心肌病大鼠中表达和磷酸化的改变 [J]. 岭南心血管病杂志， 2011 ， 17 ( 3 )： 228 - 231，254 .

娄雪林，徐涛，周专．胰腺 β 细胞的离子通道和胰岛素分泌 [J]．生命的化学， 2001 ， 21 ( 2 )： 150 - 152 .

M Ferron , E Hinoi , G Karsenty , et al . Osteocalcin differentially regulates A cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice [J]. Proc Natl Acad Sci USA , 2008 ， 105 ( 13 )： 5266 - 5270 .

T Yamauchi ， J Kamon ， H Waki ， et al . The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity [J]. Nat Med ， 2001 ， 7 ( 8 )： 941 - 946 .

Y C Hwang , I K Jeong , K J Ahn , et al . The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects [J]. Diabetes Metab Res Rev ， 2009 ， 25 ( 8 )： 768 - 772 .

李连涛，林丽香，陈刚，等 . NF- κ B信号通路对糖尿病血管内皮的影响 [J]．福建医药杂志， 2017 ， 39 ( 6 )： 14 - 19 .

M L Sheu , F M Ho , K F CHAO , et al . Activation of phosphoinositide 3-kinase in response to high glucose leads to regulation of reactive oxygen species-related nuclear factor-kappaB activation and cyclooxygenase-2 expression in mesangial cells [J]. Mol Pharmacol , 2004 ， 66 ( 1 )： 187 - 196 .

赵曼．黄连素治疗慢性乙型肝炎合并胆囊炎前后的血清细胞因子的变化 [C]∥ 湖南中医药大学学报2016/专集：国际数字医学会数字中医药分会成立大会暨首届数字中医药学术交流会论文集，珠海， 2016 ： 121 - 122 .

封芬，谭安雄，邓集湘．黄连素对2型糖尿病大鼠胸主动脉PI3K/Akt/eNOS信号通路的影响 [J]．中国当代医药， 2018 ， 25 ( 30 )： 12 - 19 .

王建礼，杨作成，王聪，等．槲皮素对糖尿病大鼠的降糖作用及机制研究 [J]．济宁医学院学报， 2018 ， 41 ( 2 )： 135 - 138 .

李海禹，孟哲，王琛，等．槲皮素对氧化低密度脂蛋白诱导的血管平滑肌细胞炎症反应的影响 [J]．中国合理用药探索， 2018 ， 15 ( 3 )： 29 - 33 .

霍梦露，王瑞瑶，李超，等．小檗碱对高糖高脂饲料联合链脲佐菌素诱导的糖尿病心肌病大鼠的保护作用 [J]．中国临床保健杂志， 2019 ， 22 ( 3 )： 377 - 382 .

李爱云，钟丛丛，张宁．小檗碱抑制NF- κ B p65改善肝脏糖异生的作用研究 [J]．中华中医药杂志， 2019 ， 34 ( 5 )： 1956 - 1960 .

王静，陈悦，袁子民．黄连胆汁炙前后对热证模型大鼠血清甲状腺激素水平和体温的影响 [J]．中国现代应用药学， 2015 ， 32 ( 12 )： 1417 - 1419 .

郭阳艳，刘萌萌，杨晓华，等 . 黄芩素对大鼠胰岛素分泌的作用及机制研究 [J]．中国药理学通报， 2018 ， 34 ( 6 )： 820 - 824 .

Y LU , L C KONG , Z H ZHANG . Baicalein protects rat cardiac myocytes from hypoxia/reoxygenation induced apoptosis via antioxidant and modulation of intracellular calcium concentration [J]. Chin J Tissue Eng Res ， 2012 ， 16 ( 50 )： 9425 - 9430 .

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