Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin Ⅱ Formula (冠心Ⅱ号方) for Coronary Heart Disease

Song SHENG; Zhi-xu YANG; Feng-qin XU; Ye HUANG

doi:10.1007/s11655-020-3199-z

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Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin Ⅱ Formula (冠心Ⅱ号方) for Coronary Heart Disease

Original Article | Updated：2021-08-16

- Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin Ⅱ Formula (冠心Ⅱ号方) for Coronary Heart Disease
- Chinese Journal of Integrative Medicine Vol. 27, Issue 2, Pages: 106-114(2021)
- Affiliations：
  
  1.Emergency Department, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing (100091), China
  2.Institute of Geriatrics, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing (100091), China
- Author bio：
  
  Correspondence to: Dr. HUANG Ye, E-mail: yellow_926@126.com
- Funds：
- DOI：10.1007/s11655-020-3199-z
  CLC：
- Published：01 February 2021，
  
  Published Online：09 May 2020，
  
  Accepted：09 March 2020
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Song SHENG, Zhi-xu YANG, Feng-qin XU, et al. Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin Ⅱ Formula (冠心Ⅱ号方) for Coronary Heart Disease. [J]. Chinese Journal of Integrative Medicine 27(2):106-114(2021)
DOI：

Song SHENG, Zhi-xu YANG, Feng-qin XU, et al. Network Pharmacology-Based Exploration of Synergistic Mechanism of Guanxin Ⅱ Formula (冠心Ⅱ号方) for Coronary Heart Disease. [J]. Chinese Journal of Integrative Medicine 27(2):106-114(2021) DOI： 10.1007/s11655-020-3199-z.

摘要

Abstract

Objective:

To study the pharmacological mechanism of Guanxin Ⅱ formula (冠心Ⅱ号方

GX Ⅱ) for treatment of coronary heart disease (CHD).

Methods:

A network pharmacology-based method was utilized. First candidate compounds

targets of GX Ⅱ were collected using PharmMapper

BATMAN-TCM

DrugBank and SwissTargetPrediction

and targets on CHD were mined from GeneCards

DisGenet

DrugBank and GEO. Afterwards

the big hub compounds and targets were chosen in the candidate compounds-direct therapeutic targets on the CHD (C-T) network and the direct therapeutic targets on the CHD (T-D) network. Furthermore

the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed to identify the enriched terms. Finally

a molecular docking simulation strategy was adopted to verify the binding capacity between the big hub compounds and big hub targets on CHD.

Results:

First

114 candidate compounds were selected with the following criteria: OB 30%

DL 0.18

and HL 4 h. Then

035 targets of GX Ⅱ were gathered

while 928 targets on CHD were collected. Afterwards

196 common targets of compound targets and therapeutic targets on CHD were defined as direct therapeutic targets acting on CHD. In addition

the contribution index (CI) in the C-T network was calculated

and 4 centrality properties

including degree

betweenness

closeness and coreness

in the T-D network

4 big hub compounds

and 6 big hub targets were eventually chosen. Furthermore

the GO and KEGG analysis indicated that GX Ⅱ acted on CHD by regulating the reactive oxygen species metabolism

steroid metabolism

lipid metabolism

inflammatory response

proliferation

differentiation and apoptosis. The docking results manifested excellent binding capacity between the 4 big hub compounds and 6 big hub targets on CHD.

Conclusion:

This network pharmacology-based exploration revealed that GX Ⅱ might prevent and inhibit the primary pathological processes of CHD.

关键词

Keywords

network pharmacologyGuanxin Ⅱ formulaChinese medicinecoronary heart diseasemolecular docking

references

Zhao D, Liu J, Wang M, Zhang X, Zhou M. Epidemiology of cardiovascular disease in China: current features and implications. Nat Rev Cardiol 2019;16:203-212.

Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A.Epidemiology of coronary heart disease and acute coronary syndrome. Ann Transl Med 2016;4:256-226.

Benjamin EJ, Muntner P, Alonso A, Bittencourt MS,Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2019 update: a report From the American Heart Association. Circulation 2019;139:e56-e528.

Chen KJ, Qian ZZ, Liu WL. Observation on long-term effects of Guanxin Ⅱ in treating 164 patients with angina pectoris of coronary heart disease. J Cardiovasc Dis (Chin) 1978;6:22-24.

Huang X, Qin F, Zhang HM, Xiao HB, Wang LX, Zhang XY, et al. Cardioprotection by Guanxin Ⅱ in rats with acute myocardial infarction is related to its three compounds. J Ethnopharmacol 2009;121:268-273.

Zhao J, Huang X, Tang W, Ren P, Xing Z, Tian X, et al. Effect of oriental herbal prescription Guan-Xin-Er-Hao on coronary flow in healthy volunteers and antiapoptosis on myocardial ischemia-reperfusion in rat models. Phytother Res 2007;21:926-931.

Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP:a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014;6:13.

Wang X, Shen Y, Wang S, Li S, Zhang W, Liu X, et al.PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res 2017;45:W356-W360.

Liu Z, Guo F, Wang Y, Li C, Zhang X, Li H, et al. BATMAN-TCM: a bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine. Sci Rep 2016;6:21146.

Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 2019;47:W357-W364.

Wishart DS, Feunang YD, Guo AC, Lo E J, Marcu A, Grant J R,et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 2018;46:D1074-D1082.

Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M,Fishilevich S, et al. The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 2016;54:1.30.31-31.30.33.

Pinero J, Bravo A, Queralt-Rosinach N, Gutierrez-Sacristan A,Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 2017;45:D833-D839.

Wu J, Chen ZP, Shang AQ, Wang WW, Chen ZN, Tao YJ, et al. Systemic bioinformatics analysis of recurrent aphthous stomatitis gene expression profiles. Oncotarget 2017;8:111064-111072.

Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY.cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Systems Bio 2014;8:S11.

Yue SJ, Liu J, Feng WW, Zhang FL, Chen JX, Xin LT, et al.System pharmacology-based dissection of the synergistic mechanism of Huangqi and Huanglian for diabetes mellitus.Front Pharmacol 2017;8:694.

Ashtiani M, Salehzadeh-Yazdi A, Razaghi-Moghadam Z,Hennig H, Wolkenhauer O, Mirzaie M, et al. A systematic survey of centrality measures for protein-protein interaction networks. BMC Syst Biol 2018;12:80.

Zhang Y, Li Y, Mao X, Yan C, Guo X, Guo Q, et al. Thyroid hormone synthesis: a potential target of a Chinese herbal formula Haizao Yuhu Decoction acting on iodine-deficient goiter. Oncotarget 2016;7:51699-51712.

Yu G, Zhang Y, Ren W, Dong L, Li J, Geng Y, et al. Network pharmacology-based identification of key pharmacological pathways of Yin-Huang-Qing-Fei capsule acting on chronic bronchitis. Int J Chron Obstruct Pulmon Dis 2017;12:85-94.

Yang J M, Chen CC. GEMDOCK: a generic evolutionary method for molecular docking. Proteins 2004;55:288-304.

Burley SK, Berman HM, Bhikadiya C, Bi C, Chen L, Di Costanzo L, et al. RCSB Protein Data Bank: biological macromolecular structures enabling research and education in fundamental biology, biomedicine, biotechnology and energy. Nucleic Acids Res 2019;47:D464-D474.

Al-Numair KS, Veeramani C, Alsaif MA, Chandramohan G. Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharm Biol 2015;53:1372-1378.

Yoon HY, Lee EG, Lee H, Cho IJ, Choi YJ, Sung MS, et al. Kaempferol inhibits IL-1beta-induced proliferation of rheumatoid arthritis synovial fibroblasts and the production of COX-2, PGE2 and MMPs. Int J Mol Med 2013;32:971-977.

Xiao J, Sun GB, Sun B, Wu Y, He L, Wang X, et al.Kaempferol protects against doxorubicin-induced cardiotoxicity in vivo and in vitro. Toxicology 2012;292:53-62.

Alkhalidy H, Moore W, Zhang Y, McMillan R, Wang A, Ali M,et al. Small molecule kaempferol promotes insulin sensitivity and preserved pancreatic beta-cell mass in middle-aged obese diabetic mice. J Diabetes Res 2015;2015:532984.

Li B, Yang M, Liu JW, Yin GT. Protective mechanism of quercetin on acute myocardial infarction in rats. Genet Mol Res 2016;15:15017117.

Domiciano TP, Wakita D, Jones HD, Crother TR, Verri WA, Jr.,Arditi M, et al.Quercetin inhibits inflammasome activation by interfering with ASC oligomerization and prevents interleukin-1 mediated mouse vasculitis. Sci Rep 2017;7:41539.

Ibarra M, Perez-Vizcaino F, Cogolludo A, Duarte J,Zaragoza-Arnaez F, Lopez-Lopez JG, et al. Cardiovascular effects of isorhamnetin and quercetin in isolated rat and porcine vascular smooth muscle and isolated rat atria.Planta Med 2002;68:307-310.

Jones PJ, MacDougall DE, Ntanios F, Vanstone CA.Dietary phytosterols as cholesterol-lowering agents in humans. Can J Physiol Pharmacol 1997;75:217-227.

Fassbender K, Lutjohann D, Dik MG, Bremmer M, Konig J, Walter S, et al. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk—the LASA study. Atherosclerosis 2008;196:283-288.

Brown RA, Shantsila E, Varma C, Lip GY. Current understanding of atherogenesis. Am J Med 2017;130:268-282.

Sarwar N, Butterworth AS, Freitag D F, Gregson J, Willeit P, Gorman DN, et al. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 2012;379:1205-1213.

Zhou S Y, Duan XQ, Hu R, Ouyang XY. Effect of non-surgical periodontal therapy on serum levels of TNF-α, IL-6 and C-reactive protein in periodontitis subjects with stable coronary heart disease. Chin J Dent Res (Chin) 2013;16:145-151.

Bennett MR, Sinha S, and Owens GK. Vascular smooth muscle cells in atherosclerosis. Circ Res 2016;118:692-702.

Zeboudj L, Maitre M, Guyonnet L, Laurans L, Joffre J,Lemarie J, et al. Selective EGF-receptor inhibition in CD4+T cells induces anergy and limits atherosclerosis. J Am Coll Cardiol 2018;71:160-172.

Monnier L, Hanefeld M, Schnell O, Colette C, Owens D.Insulin and atherosclerosis: how are they related? Diabetes Metab 2013;39:111-117.

Mishra B, Pandey S, Niraula SR, Rai BK, Karki P, Baral N, et al. Utility of ischemia modified albumin as an early marker for diagnosis of acute coronary syndrome. J Nepal Health Res Counc 2018;16:16-21.

Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC. Inflammatory cytokines in atherosclerosis: current therapeutic approaches. Eur Heart J 2016;37:1723-1732.

Linton MF, Babaev VR, Huang J, Linton EF, Tao H,Yancey PG. Macrophage apoptosis and efferocytosis in the pathogenesis of atherosclerosis. Circ J 2016;80:2259-2268.

Zhang XY, Huang X, Ren P, Xu DY, Zhang Y, Luo SS, et al.The cardio-protection mechanism research on anti-apoptosis and anti-inflammation of Chinese compound formula Guanxin No.2. In: The Sixth National Academic Seminar on Basic Theoretical research of Chinese Association of Integrative Medicine. 2010: Changsha, Hunan, China.

Huang X, Zhang XY, Qin F, Wang XY, Ren P, Liu ZQ, et al.Pretreatment with a traditional Chinese formula, GuanxinⅡ, reduces cardiac apoptosis via the Akt survival pathway in rats with myocardial ischemia. Tohoku J Exp Med 2010;220:157-163.

Wang YG. Effects of traditional Chineses herb remedies Guan-Xin-Er-Hao and Xiong-Shao on hemodynamics and their preliminary protective mechanism of vascular endothelium in anesthetized rats [dissertation]. Chengdu: West China School of Medicine, Sichuan University; 2007.

Yang HB, Wang CL, Wu SJ. The effect of Guanxin Ⅱ Hao on plasma SOD, CRP and MDA in myocardial ischemia dog. Chin J Inf Tradit Chin Med (Chin) 2005;12:19-20.

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The Second Clinical Medical College, Guangzhou University of Chinese Medicine

Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine

Faculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology

Key Laboratory of Cosmetics Monitoring and Evaluation, State Drug Administration, Shenzhen Institute for Drug Control

The School of Basic Medical Sciences, Hubei University of Chinese Medicine

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