Drug Target Prediction Based on the Herbs Components: the Study on the Multitargets Pharmacological Mechanism of Qishenkeli Acting on the Coronary Heart Disease

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2012 Apr 5

PMID 22474514

Citations 52

Authors

Yong Wang

Zhongyang Liu

Chun Li

Dong Li

Yulin Ouyang

Junda Yu

Shuzhen Guo

Fuchu He

Wei Wang

Affiliations

Soon will be listed here.

Abstract

In this paper, we present a case study of Qishenkeli (QSKL) to research TCM's underlying molecular mechanism, based on drug target prediction and analyses of TCM chemical components and following experimental validation. First, after determining the compositive compounds of QSKL, we use drugCIPHER-CS to predict their potential drug targets. These potential targets are significantly enriched with known cardiovascular disease-related drug targets. Then we find these potential drug targets are significantly enriched in the biological processes of neuroactive ligand-receptor interaction, aminoacyl-tRNA biosynthesis, calcium signaling pathway, glycine, serine and threonine metabolism, and renin-angiotensin system (RAAS), and so on. Then, animal model of coronary heart disease (CHD) induced by left anterior descending coronary artery ligation is applied to validate predicted pathway. RAAS pathway is selected as an example, and the results show that QSKL has effect on both rennin and angiotensin II receptor (AT1R), which eventually down regulates the angiotensin II (AngII). Bioinformatics combing with experiment verification can provide a credible and objective method to understand the complicated multitargets mechanism for Chinese herbal formula.

Citing Articles

A Comprehensive Review on Potential In Silico Screened Herbal Bioactive Compounds and Host Targets in the Cardiovascular Disease Therapy.

Zarenezhad E, Hadi A, Nournia E, Rostamnia S, Ghasemian A Biomed Res Int. 2024; 2024:2023620.

PMID: 39502274 PMC: 11537750. DOI: 10.1155/2024/2023620.

Time-dependent specific molecular signatures of inflammation and remodelling are associated with trimethylamine-N-oxide (TMAO)-induced endothelial cell dysfunction.

Shanmugham M, Devasia A, Chin Y, Cheong K, Ong E, Bellanger S Sci Rep. 2023; 13(1):20303.

PMID: 37985702 PMC: 10661905. DOI: 10.1038/s41598-023-46820-7.

Qishen granules regulate intestinal microecology to improve cardiac function in rats with heart failure.

Gao K, Yu X, Li F, Huang Y, Liu J, Liu S Front Microbiol. 2023; 14:1202768.

PMID: 37396388 PMC: 10307979. DOI: 10.3389/fmicb.2023.1202768.

Potential Targets and Mechanisms of Jiedu Quyu Ziyin Decoction for Treating SLE-GIOP: Based on Network Pharmacology and Molecular Docking.

Li J, Chang R, Chen L, Qian S, Wang R, Lan J J Immunol Res. 2023; 2023:8942415.

PMID: 37026113 PMC: 10072964. DOI: 10.1155/2023/8942415.

Study on the Action Mechanism of the Yifei Jianpi Tongfu Formula in Treatment of Colorectal Cancer Lung Metastasis Based on Network Analysis, Molecular Docking, and Experimental Validation.

Zhu W, Zhang R, Ma C, Hu Y, Shi X, Wang X Evid Based Complement Alternat Med. 2022; 2022:6229444.

PMID: 35942366 PMC: 9356795. DOI: 10.1155/2022/6229444.

References

Salwinski L, Miller C, Smith A, Pettit F, Bowie J, Eisenberg D . The Database of Interacting Proteins: 2004 update. Nucleic Acids Res. 2003; 32(Database issue):D449-51. PMC: 308820. DOI: 10.1093/nar/gkh086. View

Tu E, Zhou Y, Wang Z, Liang Q, Yang G . Effects of tanshinone II A on the myocardial hypertrophy signal transduction system protein kinase B in rats. Chin J Integr Med. 2009; 15(5):365-70. DOI: 10.1007/s11655-009-0365-8. View

Mehta P, Griendling K . Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2006; 292(1):C82-97. DOI: 10.1152/ajpcell.00287.2006. View

He J, Gu D, Wu X, Reynolds K, Duan X, Yao C . Major causes of death among men and women in China. N Engl J Med. 2005; 353(11):1124-34. DOI: 10.1056/NEJMsa050467. View

Stark C, Breitkreutz B, Reguly T, Boucher L, Breitkreutz A, Tyers M . BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 2005; 34(Database issue):D535-9. PMC: 1347471. DOI: 10.1093/nar/gkj109. View

Keshava Prasad T, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S . Human Protein Reference Database--2009 update. Nucleic Acids Res. 2008; 37(Database issue):D767-72. PMC: 2686490. DOI: 10.1093/nar/gkn892. View

Nidhi , Glick M, Davies J, Jenkins J . Prediction of biological targets for compounds using multiple-category Bayesian models trained on chemogenomics databases. J Chem Inf Model. 2006; 46(3):1124-33. DOI: 10.1021/ci060003g. View

Barbe F, Su J, Guyene T, Crozatier B, Menard J, Hittinger L . Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure. Am J Physiol. 1996; 270(6 Pt 2):H1985-92. DOI: 10.1152/ajpheart.1996.270.6.H1985. View

Xu H, Chen K . Herb-drug interaction: an emerging issue of integrative medicine. Chin J Integr Med. 2010; 16(3):195-6. DOI: 10.1007/s11655-010-0195-z. View

10.

Parsons A, Brost R, Ding H, Li Z, Zhang C, Sheikh B . Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol. 2003; 22(1):62-9. DOI: 10.1038/nbt919. View

11.

Bender A, Mussa H, Glen R, Reiling S . Molecular similarity searching using atom environments, information-based feature selection, and a naïve Bayesian classifier. J Chem Inf Comput Sci. 2004; 44(1):170-8. DOI: 10.1021/ci034207y. View

12.

Rousseau M, Konstam M, Benedict C, Donckier J, Galanti L, Melin J . Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor. Am J Cardiol. 1994; 73(7):488-93. DOI: 10.1016/0002-9149(94)90680-7. View

13.

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

14.

Neutel J . Choosing among renin-angiotensin system blockers for the management of hypertension: from pharmacology to clinical efficacy. Curr Med Res Opin. 2009; 26(1):213-22. DOI: 10.1185/03007990903444434. View

15.

Basile J, Toth P . Angiotensin receptor blockers: role in hypertension management, cardiovascular risk reduction, and nephropathy. South Med J. 2009; 102(10 Suppl):S1-S12. DOI: 10.1097/SMJ.0b013e3181ba0d8a. View

16.

Beierwaltes W . The role of calcium in the regulation of renin secretion. Am J Physiol Renal Physiol. 2009; 298(1):F1-F11. PMC: 2806121. DOI: 10.1152/ajprenal.00143.2009. View

17.

Cain A, Tanner D, Khalil R . Endothelin-1--induced enhancement of coronary smooth muscle contraction via MAPK-dependent and MAPK-independent [Ca(2+)](i) sensitization pathways. Hypertension. 2002; 39(2 Pt 2):543-9. DOI: 10.1161/hy0202.103129. View

18.

Gibson T, Goldberg D . Questioning the ubiquity of neofunctionalization. PLoS Comput Biol. 2009; 5(1):e1000252. PMC: 2597716. DOI: 10.1371/journal.pcbi.1000252. View

19.

Dai G, Zhang B, Guo Z . [Application of central randomized system in project of clinical trial for secondary prevention of myocardial infarction by Qishen Yiqi Drop Pill]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007; 27(7):653-6. View

20.

Chen W, Yu M, Li Y, Chen W, Xia Y . Beneficial effects of astragalus polysaccharides treatment on cardiac chymase activities and cardiomyopathy in diabetic hamsters. Acta Diabetol. 2009; 47 Suppl 1:35-46. DOI: 10.1007/s00592-009-0116-5. View