Advanced Search

Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 1: 131 - 144

DOI: https://doi.org/10.19852/j.cnki.jtcm.20231121.003

Original articles

Efficacy of Danlou tablet (丹蒌片) on myocardial ischemia/ reperfusion injury assessed by network pharmacology and experimental verification

  • Ye YANG ,
  • Xiaoyang CHEN ,
  • Junkai YAO ,
  • Yueyao HU ,
  • Wei WANG
Expand
  • 1 School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100700, China
    2 School of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

Received date: 2022-10-11

  Accepted date: 2023-01-15

  Online published: 2023-11-21

Fold

Abstract

OBJECTIVE: To investigate the potential pharmacological mechanism of Danlou tablet (丹蒌片, DLT) with a long-term clinical application in the treatment of myocardial ischemia/reperfusion (I/R) injury through network pharmacology, molecular docking and experimental verification.

METHODS: The main chemical ingredients in DLT were retrieved from the Traditional Chinese Medicine (TCM) System Pharmacology Database, the TCM information database, the bioinformatics analysis tool for molecular mechanism of TCM, and HERB database. Disease targets of I/R were accessed from the databases of Online Mendelian Inheritance in Man, GeneCards, Therapeutic Target Database, and DisGeNET database. The overlaying genes of DLT and I/R were obtained from the Venny online platform. The core targets and protein-protein interaction network were constructed and analyzed via the Search Tool for the Retrieval of Interacting Genes Proteins database and Cytoscape software. Furthermore, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Metascape platform. Based on the results, the component-target-pathway network was constructed and drafted via the Cytoscape software and the platform of Bioinformatics. Furthermore, we performed molecular docking to predict the binding information between chemical molecules and target proteins. Finally, oxygen-glucose deprivation/recovery (OGD/R)-induced H9c2 cardiomyocytes were used to validate the results of network pharmacology in vitro.

RESULTS: A total of 189 active chemical components in DLT and 849 correlative targets of I/R were screened. Of note, 133 overlaying genes found from the Venny online platform were concentrated into 28 core genes. Furthermore, the GO and KEGG pathway enrichment analysis presented that DLT might participate in 42 types of GO molecular functions, 747 types of GO biological processes, 19 types of GO cellular components, and 140 kinds of pathways to treat I/R. In the component-target-pathway network, the indirect relationship between herbs and their possible effective pathways was clarified. Based on the molecular docking, we speculated that Baicalein-prostaglandin G/H synthase 2 (PTGS2) with -3.24 kcal/mol, Luteolin-heat shock protein 90 alpha family class A member 1 (HSP90AA1) with -3.22 kcal/mol, Baicalein-HSP90AA1 with -3.13 kcal/mol, and Quercetin-HSP90AA1 with -3.05 kcal/mol possessed the strongest binding force of less than -3 kcal/mol, sequentially. Experimental verification showed that Quercetin, Luteolin, and Baicalein could increase the relative cell viability of OGD/R-stimulated cardiomyocytes, probably by suppressing PTGS2, and activating HSP90AA1 and estrogen receptor 1 expression.

CONCLUSIONS: We predicted the potential active compounds as the material basis of DLT that may provide a new approach to elucidate the novel pharmacological mechanism underlying the treatment of cardiac I/R damage.

Key words： myocardial ischemia; reperfusion; network pharmacology; molecular docking simulation; oxygen-glucose deprivation/recovery; Danlou tablet

Cite this article

Ye YANG , Xiaoyang CHEN , Junkai YAO , Yueyao HU , Wei WANG . Efficacy of Danlou tablet (丹蒌片) on myocardial ischemia/ reperfusion injury assessed by network pharmacology and experimental verification[J]. Journal of Traditional Chinese Medicine, 2024 , 44(1) : 131 -144 . DOI: 10.19852/j.cnki.jtcm.20231121.003

References

1. Hausenloy DJ, Botker HE, Engstrom T, et al. Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations. Eur Heart J 2017; 38: 935-41.
2. Heusch G. Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat Rev Cardiol 2020; 17: 773-89.
3. Heusch G, B?tker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol 2015; 65: 177-95.
4. Ye T, Xiong D, Li Y, et al. Inhibition of nuclear factor kappa B as a mechanism of Danshensu during toll-like receptor 2-triggered inflammation in macrophages. Int Immunopharmacol 2020; 83: 106419.
5. Wang L, Wu T, Si C, et al. Danlou tablet activates autophagy of vascular adventitial fibroblasts through PI3K/Akt/mTOR to protect cells from damage caused by atherosclerosis. Front Pharmacol 2021; 12: 730525.
6. Li Z, Yang L, Liu Y, et al. Anti-inflammatory and antioxidative effects of Danlou tablets in the treatment of coronary heart disease revealed by metabolomics integrated with molecular mechanism studies. J Ethnopharmacol 2019; 240: 111911.
7. Wei M, Guo M, Meng X, et al. PPARγ mediates the cardioprotective roles of Danlou tablet after acute myocardial ischemia-reperfusion injury. Front Cardiovasc Med 2022; 9: 858909.
8. Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13.
9. Ji ZL, Zhou H, Wang JF, Han LY, Zheng CJ, Chen YZ. Traditional Chinese Medicine information database. J Ethnopharmacol 2006; 103: 501.
10. Liu Z, Guo F, Wang Y, et al. BATMAN-TCM: a bioinformatics analysis tool for molecular mechanism of Traditional Chinese Medicine. Sci Rep 2016; 6: 21146.
11. Fang S, Dong L, Liu L, et al. HERB: a high-throughput experiment- and reference-guided database of Traditional Chinese Medicine. Nucleic Acids Res 2021; 49: D1197-206.
12. Song W, Ni S, Fu Y, Wang Y. Uncovering the mechanism of Maxing Ganshi decoction on asthma from a systematic perspective: a network pharmacology study. Sci Rep 2018; 8: 17362.
13. UniProt Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Res 2021; 49: D480-9.
14. Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks. Methods Mol Biol 2011; 696: 291-303.
15. Rasmussen SA, Hamosh A. What's in a name? Issues to consider when naming Mendelian disorders. Genet Med 2020; 22: 1573-5.
16. Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database. Oxford 2010; 2010: baq020.
17. Zhou Y, Zhang Y, Lian X, et al. Therapeutic target database update 2022: facilitating drug discovery with enriched comparative data of targeted agents. Nucleic Acids Res 2022; 50: D1398-407.
18. Pi?ero J, Saüch J, Sanz F, Furlong LI. The DisGeNET cytoscape app: exploring and visualizing disease genomics data. Comput Struct Biotechnol J 2021; 19: 2960-7.
19. Jia C, Pan X, Wang B, Wang P, Wang Y, Chen R. Mechanism prediction of against cisplatin-induced kidney damage by network pharmacology and molecular docking. Evid Based Complement Alternat Med 2021; 2021: 9516726.
20. Wei Y, Ren S, Wang R, et al. Based on network pharmacology to explore the potential bioactive compounds and mechanisms of Zuojin pill for the treatment of ulcerative colitis. Evid Based Complement Alternat Med 2021; 2021: 7567025.
21. Szklarczyk D, Gable AL, Nastou KC, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res 2021; 49: D605-12.
22. Ding Z, Xu F, Sun Q, et al. Exploring the mechanism of action of herbal medicine (decoction) for poststroke depression based on network pharmacology and molecular docking. Evid Based Complement Alternat Med 2021; 2021: 2126967.
23. Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 2019; 10: 1523.
24. Dedhia M, Kohetuk K, Crusio WE, Delprato A. Introducing high school students to the Gene Ontology classification system. F1000Res 2019; 8: 241.
25. Burenbatu, Wang Y, Wang S, et al. iTRAQ-based quantitative proteomics analysis of immune thrombocytopenia patients before and after Qishunbaolier treatment. Rapid Commun Mass Spectrom 2021; 35: e8993.
26. Seeliger D, de Groot BL. Ligand docking and binding site analysis with PyMOL and autodock/vina. J Comput Aided Mol Des 2010; 24: 417-22.
27. 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: 455-61.
28. Chang H, Li C, Wang Q, et al. QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p 53 signaling pathway. Sci Rep 2017; 7: 16986.
29. Raja-Khan N, Stener-Victorin E, Wu X, Legro RS. The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. Am J Physiol Endocrinol Metab 2011; 301.
30. Perry E, Howes M-JR. Medicinal plants and dementia therapy: herbal hopes for brain aging? CNS Neurosci Ther 2011; 17: 683-98.
31. Ding M, Ma W, Wang X, et al. A network pharmacology integrated pharmacokinetics strategy for uncovering pharmacological mechanism of compounds absorbed into the blood of Danlou tablet on coronary heart disease. J Ethnopharmacol 2019; 242: 112055.
32. Li Y, Zhao H, Du J, et al. Clinical metabolomic analysis of Danlou tablets with antioxidant effects for treating stable angina pectoris. J Pharm Biomed Anal 2022; 219: 114922.
33. Qi JY, Wang L, Gu DS, Guo LH, Zhu W, Zhang MZ. Protective effects of Danlou tablet against murine myocardial ischemia and reperfusion injury in vivo. Chin J Integr Med 2018; 24: 613-20.
34. Piot C, Croisille P, Staat P, et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 2008; 359: 473-81.
35. Tóth ?, Jonecová Z, ?urgali K, et al. Quercetin attenuates the ischemia reperfusion induced COX-2 and MPO expression in the small intestine mucosa. Biomed Pharmacother 2017; 95: 346-54.
36. Gutiérrez-Venegas G, Torras-Ceballos A, Gómez-Mora JA, Fernández-Rojas B. Luteolin, quercetin, genistein and quercetagetin inhibit the effects of lipopolysaccharide obtained from in H9c2 cardiomyoblasts. Cell Mol Biol Lett 2017; 22: 19.
37. Qin L, Chen Z, Yang L, et al. Luteolin-7-O-glucoside protects dopaminergic neurons by activating estrogen-receptor-mediated signaling pathway in MPTP-induced mice. Toxicology 2019; 426: 152256.
38. Zheng N, Yuan P, Li C, Wu J, Huang J. Luteolin reduces BACE1 expression through NF-κB and through estrogen receptor mediated pathways in HEK293 and SH-SY5Y cells. J Alzheimers Dis 2015; 45: 659-71.
39. Ji Y, Han J, Lee N, et al. Neuroprotective effects of Baicalein, Wogonin, and Oroxylin A on amyloid beta-induced toxicity via NF-κB/MAPK pathway modulation. Molecules 2020; 25: 5087.
40. Fan GW, Zhang Y, Jiang X, et al. Anti-inflammatory activity of baicalein in LPS-stimulated RAW264.7 macrophages via estrogen receptor and NF-κB-dependent pathways. Inflammation 2013; 36: 1584-91.
Options
Outlines

/

〈 〉