Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via A Network Pharmacology Approach

Zi-qi MENG; Jia-rui WU; Ying-li ZHU; Wei ZHOU; Chang-geng FU; Xin-kui LIU; Shu-yu LIU; Meng-wei NI; Si-yu GUO

doi:10.1007/s11655-020-2716-4

Your Location：

Home >

Browse articles >

Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via A Network Pharmacology Approach

Methodology Research | Updated：2021-08-16

- Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via A Network Pharmacology Approach
- Chinese Journal of Integrative Medicine Vol. 27, Issue 1, Pages: 62-69(2021)
- Affiliations：
  
  1.Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing(100029), China
  2.Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China
- Author bio：
  
  Correspondence to: Prof. WU Jia-rui, E-mail: exogamy@163.com
- Funds：
- DOI：10.1007/s11655-020-2716-4
  CLC：
- Published：01 January 2021，
  
  Published Online：22 May 2020，
  
  Accepted：28 August 2019
Scan for full text
Zi-qi MENG, Jia-rui WU, Ying-li ZHU, et al. Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via A Network Pharmacology Approach. [J]. Chinese Journal of Integrative Medicine 27(1):62-69(2021)
DOI：

Zi-qi MENG, Jia-rui WU, Ying-li ZHU, et al. Revealing the Common Mechanisms of Scutellarin in Angina Pectoris and Ischemic Stroke Treatment via A Network Pharmacology Approach. [J]. Chinese Journal of Integrative Medicine 27(1):62-69(2021) DOI： 10.1007/s11655-020-2716-4.

摘要

Abstract

Objective:

To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment.

Methods:

A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction

protein-protein interaction (PPI) data collection

network construction

network analysis

and enrichment analysis. Furthermore

molecular docking simulation was employed to analyze the interaction between scutellarin and core targets.

Results:

Two networks were established

including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets

namely

AKT1

VEGFA

JUN

ALB

MTOR

ESR1

MAPK8

HSP90AA1

NOS3

SERPINE1

FGA

FOXO3

and STAT1

might be the therapeutic targets of scutellarin in AP and IS. Among them

NOS3 and F2 were recognized as the core targets. Additionally

molecular docking simulation confirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore

enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways

such as coagulation cascades

mitogen-activated protein kinase (MAPK) signaling pathway

phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway

Toll-like receptor signaling pathway

hypoxia inducible factor-1 (HIF-1) signaling pathway

forkhead box O (FoxO) signaling pathway

tumor necrosis factor (TNF) signaling pathway

adipocytokine signaling pathway

insulin signaling pathway

insulin resistance

and estrogen signaling pathway.

Conclusions:

The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant

anticoagulant

anti-inflammatory

and antioxidative effects as well as its effect on improving lipid metabolism.

关键词

Keywords

scutellarinangina pectorisischemic strokenetwork pharmacology

references

Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 2019;139:e56-e66.

Tan D, Wu JR, Cui YY, et al. Ginkgo leaf extract and dipyridamole injection as adjuvant treatment for angina pectoris: a meta-analysis of 41 randomized controlled trials. Chin J Integr Med 2018;24:930-937.

Tan D, Wu JR, Zhang XM, et al. Sodium tanshinone ⅡA sulfonate injection as adjuvant treatment for unstable angina pectoris: a meta-analysis of 17 randomized con-trolled trials. Chin J Integr Med 2018;24:156-160.

Valdes-Marquez E, Parish S, Clarke R, et al. Relative effects of LDL-C on ischemic stroke and coronary disease: a Mendelian randomization study. Neurology 2019;92:e1176-e1187.

Gaire BP. Herbal medicine in ischemic stroke: challenges and prospective. Chin J Integr Med 2018;24:243-246.

Li XM, Wang XY, Feng XW, et al. Serum interleukin-33 as a novel marker for long-term prognosis and recurrence in acute ischemic stroke patients. Brain Behav 2019:e01369.

Sun T, Wang X, Xu H. Ginkgo Biloba extract for angina pectoris: a systematic review. Chin J Integr Med 2015;21:542-550.

Huang Y, Wang L, Mao Y, et al. Long noncoding RNA-H19 contributes to atherosclerosis and induces ischemic stroke via the upregulation of acid phosphatase 5. Front Neurol 2019;10:32.

Morishita T, Uzui H, Nakano A, et al. Association of plasma pentraxin-3 levels with coronary risk factors and the lipid profile:a cross-sectional study in Japanese patients with stable angina pectoris. Heart Vessels 2018;33:1301-1310.

Hoffmann J, Haastert B, Brune M, et al. How do patients with diabetes report their comorbidities? Comparison with administrative data. Clin Epidemiol 2018;10:499-509.

Girot M, Deplanque D, Pasquier F, et al. Comparison of secondary vascular prevention in practice after cerebral ischemia and coronary heart disease. J Neurol 2004;251:529-536.

Mo J, Yang R, Li F, et al. Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation.Phytomedicine 2018;42:66-74.

Guo LL, Guan ZZ, Huang Y, et al. The neurotoxicity of beta-amyloid peptide toward rat brain is associated with enhanced oxidative stress, inflammation and apoptosis, all of which can be attenuated by scutellarin. Exp Toxicol Pathol 2013;65:579-584.

Shi ZH, Li NG, Wang ZJ, et al. Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo. Eur J Med Chem 2015;106:95-105.

Li Q, Wu JH, Guo DJ, et al. Suppression of diet-induced hypercholesterolemia by scutellarin in rats. Planta Med 2009;75:1203-1208.

Wang W, Ma X, Han J, et al. Neuroprotective effect of scutellarin on ischemic cerebral injury by down-regulating the expression of angiotensin-converting enzyme and AT1 receptor. PLoS One 2016;11:e0146197.

Gao J, Chen G, He H, et al. Therapeutic effects of breviscapine in cardiovascular diseases: a review. Front Pharmacol 2017;8:289.

Lin LL, Liu AJ, Liu JG, et al. Protective effects of scutellarin and breviscapine on brain and heart ischemia in rats. J Cardiovasc Pharmacol 2007;50:327-332.

Muhammad J, Khan A, Ali A, et al. Network pharmacology:exploring the resources and methodologies. Curr Top Med Chem 2018;18:949-964.

Liu X, Wu J, Zhang D, et al. Network pharmacology-based approach to investigate the mechanisms of Hedyotis diffusa Willd. in the treatment of gastric cancer. Evid Based Complement Alternat Med 2018;2018:7802639.

Luo TT, Lu Y, Yan SK, et al. Network pharmacology in re-search of Chinese medicine formula: methodology, applica-tion and prospective. Chin J Integr Med 2020;26:72-80.

Wang Y, Guo G, Yang BR, et al. Synergistic effects of Chuanxiong-Chishao herb-pair on promoting angiogenesis at network pharmacological and pharmacodynamic levels. Chin J Integr Med 2017;23:654-662.

Kim S, Thiessen PA, Bolton EE, et al. PubChem Substance and Compound databases. Nucleic Acids Res 2016;44:D1202-D1213.

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

UniProt C. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res 2019;47:D506-D515.

Li YH, Yu CY, Li XX, et al. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res 2018;46:D1121-D1127.

Kohler S, Carmody L, Vasilevsky N, et al. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. Nucleic Acids Res 2019;47:D1018-D1027.

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

Liu X, Wu J, Zhang D, et al. A network pharmacology approach to uncover the multiple mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer. Evid Based Complement Alternat Med 2018;2018:6517034.

Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 2017;45:D362-D368.

Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-2504.

Liu H, Zeng L, Yang K, et al. A network pharmacology approach to explore the pharmacological mechanism of Xiaoyao Powder on anovulatory infertility. Evid Based Complement Alternat Med 2016;2016:2960372.

Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 2003;4:2.

Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.Nat Protoc 2009;4:44-57.

Berman HM, Westbrook J, Feng Z, et al. The protein data bank.Nucleic Acids Res 2000;28:235-242.

Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 2009;30:2785-2791.

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-461.

Lin H, Zhang W, Dong ZX, et al. A new and practical synthetic method for the synthesis of 6-O-methyl-scutellarein: one metabolite of scutellarinin vivo. Int J Mol Sci 2015;16:7587-7594.

Nassar BA, Bevin LD, Johnstone DE, et al. Relationship of the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and early-onset coronary artery disease. Am Heart J 2001;142:586-589.

Luizon MR, Pereira DA, Tanus-Santos JE. Pharmacogenetic relevance of endothelial nitric oxide synthase polymorphisms and gene interactions. Pharmacogenomics 2018;19:1423-1435.

Johns R, Chen ZF, Young L, et al. Meta-analysis of NOS3 G894T polymorphisms with air pollution on the risk of ischemic heart disease worldwide. Toxics 2018;6:pii:E44.

Rai H, Parveen F, Kumar S, et al. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review. PLoS One 2014;9:e113363.

Yoshimura T, Hisatomi A, Kajihara S, et al. The relationship between insulin resistance and polymorphisms of the endothelial nitric oxide synthase gene in patients with coronary artery disease. J Atheroscler Thromb 2003;10:43-47.

Glueck CJ, Munjal J, Khan A, et al. Endothelial nitric oxide synthase T-786C mutation, a reversible etiology of Prinzmetal's angina pectoris.Am J Cardiol 2010;105:792-796.

Mao M, Sudhahar V, Ansenberger-Fricano K, et al. Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. Free Radic Biol Med 2012;52:427-435.

Fan H, Ma X, Lin P, et al. Scutellarin prevents nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia via PI3K/AKT-dependent activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in rats. Med Sci Monit 2017;23:5599-5612.

Chinnaraj M, Planer W, Pozzi N. Structure of coagulation factor Ⅱ:molecular mechanism of thrombin generation and development of next-generation anticoagulants. Front Med (Lausanne) 2018;5:281.

Gong G, Qin Y, Huang W. Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo.Phytomedicine 2011;18:458-463.

Yildiz BS, Bilgin M, Zungur M, et al. Manual thrombus aspiration and the improved survival of patients with unstable angina pectoris treated with percutaneous coronary intervention (30 months follow-up). Medicine(Baltimore) 2016;95:e2919.

Kraft P, Schwarz T, Meijers JC, et al. Thrombin-activatable fibrinolysis inhibitor (TAFI) deficient mice are susceptible to intracerebral thrombosis and ischemic stroke. PLoS One 2010;5:e11658.

Wilson SJ, Connolly TM, Peters G, et al. Exosite 1 thrombin inhibition with JNJ-64179375 inhibits thrombus formation in a human translational model of thrombosis. Cardiovasc Res 2019;115:669-677.

Machida T, Dohgu S, Takata F, et al. Role of thrombin-PAR1-PKC theta/delta axis in brain pericytes in thrombin-induced MMP-9 production and blood-brain barrier dysfunction in vitro. Neuroscience 2017;350:146-157.

Zhang X, Guan J, Zhu H, et al. Simultaneous determination of scutellarin and tetrahydropalmatine of Deng-yan Granule in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 2014;971:126-132.

Lu L, Qin Y, Chen C, et al. Beneficial effects exerted by paeonol in the management of atherosclerosis. Oxid Med Cell Longev 2018;2018:1098617.

Ozkaramanli Gur D, Guzel S, Akyuz A, et al. The role of novel cytokines in inflammation: defining peripheral artery disease among patients with coronary artery disease. Vasc Med 2018;23:428-436.

Cui X, Qian DW, Jiang S, et al. Scutellariae Radix and Coptidis Rhizoma improve glucose and lipid metabolism in T2DM rats via regulation of the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Int J Mol Sci 2018;19:pii:E3634.

Fei X, Yuan W, Zhao Y, et al. Papain ameliorates the MPAs formation-mediated activation of monocytes by inhibiting Cox-2 expression via regulating the MAPKs and PI3K/Akt signal pathway.Biomed Res Int 2018;2018:3632084.

Gao W, Xiong Y, Li Q, et al. Inhibition of Toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to Nano therapeutics. Front Physiol 2017;8:508.

Polykratis A, van Loo G, Xanthoulea S, et al. Conditional targeting of tumor necrosis factor receptor-associated factor 6 reveals opposing functions of Toll-like receptor signaling in endothelial and myeloid cells in a mouse model of atherosclerosis. Circulation 2012;126:1739-1751.

Yuan Y, Fang M, Wu CY, et al. Scutellarin as a potential therapeutic agent for microglia-mediated neuroinflammation in cerebral ischemia.Neuromolecular Med 2016;18:264-273.

Husain K, Hernandez W, Ansari RA, et al. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem 2015;6:209-217.

Zhang Y, Zhong P, Xu Y, et al. Differential expression of TXNIP isoforms in the peripheral leukocytes of patients with acute myocardial infarction. Dis Markers 2018;2018:9051481.

Belaidi E, Morand J, Gras E, et al. Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the treatment of obstructive sleep apnea-related cardiovascular complications.Pharmacol Ther 2016;168:1-11.

Wang D, Wang L, Gu J, et al. Scutellarin inhibits high glucose-induced and hypoxia-mimetic agent-induced angiogenic effects in human retinal endothelial cells through reactive oxygen species/hypoxia-inducible factor-1alpha/vascular endothelial growth factor pathway. J Cardiovasc Pharmacol 2014;64:218-227.

Zhou P, Lu S, Luo Y, et al. Attenuation of TNF-alpha-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-kappaB, JNK and p38 signaling pathways. Front Pharmacol 2017;8:464.

Gong J, Zhang L, Zhang Q, et al. Lentiviral vector-mediated SHC3 silencing exacerbates oxidative stress injury in nigral dopamine neurons by regulating the PI3K-AKT-FoxO signaling pathway in rats with Parkinson's disease. Cell Physiol Biochem 2018;49:971-984.

Duan J, Liang S, Feng L, et al. Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro. Int J Nanomed 2018;13:7303-7318.

Avramoglu RK, Basciano H, Adeli K. Lipid and lipoprotein dysregulation in insulin resistant states. Clin Chim Acta 2006;368:1-19.

Pandeya PR, Lamichhane R, Lee KH, et al. Bioassay-guided isolation of active anti-adipogenic compound from royal jelly and the study of possible mechanisms. BMC Complement Altern Med 2019;19:33.

Ito S, Nagoshi T, Minai K, et al. Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis. PLoS One 2017;12:e0176435.

Laakso M, Lehto S, Penttila I, et al. Lipids and lipoproteins predicting coronary heart disease mortality and morbidity in patients with non-insulin-dependent diabetes. Circulation 1993;88:1421-1430.

Zhang Y, Ren P, Kang Q, et al. Effect of tetramethylpyrazine on atherosclerosis and SCAP/SREBP-1c signaling pathway in ApoE(-/-) mice fed with a high-fat diet. Evid Based Complement Alternat Med 2017;2017:3121989.

Sukocheva O, Wadham C, Gamble J, et al. Sphingosine-1-phosphate receptor 1 transmits estrogens' effects in endothelial cells. Steroids 2015;104:237-245.

Zhu JT, Choi RC, Chu GK, et al. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells:a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J Agric Food Chem 2007;55:2438-2445.

Zhu JT, Choi RC, Li J, et al. Estrogenic and neuroprotective properties of scutellarin from Erigeron breviscapus: a drug against postmenopausal symptoms and Alzheimer's disease. Planta Med 2009;75:1489-1493.

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Kuanxiong Aerosol (宽胸气雾剂) in Treatment of Angina Pectoris: A Literature Review and Network Pharmacology

Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues

Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

Analysis of Chinese Medical Syndrome Features of Ischemic Stroke Based on Similarity of Symptoms Subgroup

Therapeutic Mechanism of Kai Xin San on Alzheimer's Disease Based on Network Pharmacology and Experimental Validation

Related Author

No data

Related Institution

The Second Clinical College of Guangzhou University of Chinese Medicine

Department of Critical Care Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

Division of Chest Pain Center, Guangdong Provincial Hospital of Chinese Medicine

Shanxi Key Laboratory of Traditional Herbal Medicines Processing, Shanxi University of Chinese Medicine

Korean Medicine R&D Center, Dongguk University

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰