System-level Multi-target Drug Discovery from Natural Products with Applications to Cardiovascular Diseases

Overview

Journal Mol Divers

Date 2014 May 6

PMID 24792224

Citations 17

Authors

Chunli Zheng

Jinan Wang

Jianling Liu

Mengjie Pei

Chao Huang

Yonghua Wang

Affiliations

Soon will be listed here.

Abstract

The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

Citing Articles

Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Mechanism of Gualou Xiebai Banxia Decoction against Myocardial Infarction.

Wang W, Chen Y Genes (Basel). 2024; 15(4).

PMID: 38674327 PMC: 11048873. DOI: 10.3390/genes15040392.

Pharmacogenomic Analysis of Combined Therapies against Glioblastoma Based on Cell Markers from Single-Cell Sequencing.

Liu J, Wu R, Yuan S, Kelleher R, Chen S, Chen R Pharmaceuticals (Basel). 2023; 16(11).

PMID: 38004399 PMC: 10675611. DOI: 10.3390/ph16111533.

Investigation of the mechanism of the anti-cancer effects of Schischkin Schott (A&P) on melanoma network pharmacology and experimental verification.

Wang F, Bai J, Li F, Liu J, Wang Y, Li N Front Pharmacol. 2022; 13:895738.

PMID: 36034875 PMC: 9411814. DOI: 10.3389/fphar.2022.895738.

Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids.

Han Y, Shi J, Xu Z, Zhang Y, Cao X, Yu J Front Pharmacol. 2022; 13:802168.

PMID: 36034794 PMC: 9399411. DOI: 10.3389/fphar.2022.802168.

The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes.

Kell D Molecules. 2021; 26(18).

PMID: 34577099 PMC: 8470029. DOI: 10.3390/molecules26185629.

References

Smoot M, Ono K, Ruscheinski J, Wang P, Ideker T . Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010; 27(3):431-2. PMC: 3031041. DOI: 10.1093/bioinformatics/btq675. View

Xiong X, Yang X, Liu Y, Zhang Y, Wang P, Wang J . Chinese herbal formulas for treating hypertension in traditional Chinese medicine: perspective of modern science. Hypertens Res. 2013; 36(7):570-9. PMC: 3703711. DOI: 10.1038/hr.2013.18. View

Pujol A, Mosca R, Farres J, Aloy P . Unveiling the role of network and systems biology in drug discovery. Trends Pharmacol Sci. 2010; 31(3):115-23. DOI: 10.1016/j.tips.2009.11.006. View

Wang X, Xu X, Li Y, Li X, Tao W, Li B . Systems pharmacology uncovers Janus functions of botanical drugs: activation of host defense system and inhibition of influenza virus replication. Integr Biol (Camb). 2012; 5(2):351-71. PMC: 7108588. DOI: 10.1039/c2ib20204b. View

WEBB N, Bottomley M, Watson C, Brenchley P . Vascular endothelial growth factor (VEGF) is released from platelets during blood clotting: implications for measurement of circulating VEGF levels in clinical disease. Clin Sci (Lond). 1998; 94(4):395-404. DOI: 10.1042/cs0940395. View

Fan H, Fu F, Yang M, Xu H, Zhang A, Liu K . Antiplatelet and antithrombotic activities of salvianolic acid A. Thromb Res. 2010; 126(1):e17-22. DOI: 10.1016/j.thromres.2010.04.006. View

Yamanishi Y, Kotera M, Kanehisa M, Goto S . Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework. Bioinformatics. 2010; 26(12):i246-54. PMC: 2881361. DOI: 10.1093/bioinformatics/btq176. View

Bai J, Abernethy D . Systems pharmacology to predict drug toxicity: integration across levels of biological organization. Annu Rev Pharmacol Toxicol. 2012; 53:451-73. DOI: 10.1146/annurev-pharmtox-011112-140248. View

Xie L, Evangelidis T, Xie L, Bourne P . Drug discovery using chemical systems biology: weak inhibition of multiple kinases may contribute to the anti-cancer effect of nelfinavir. PLoS Comput Biol. 2011; 7(4):e1002037. PMC: 3084228. DOI: 10.1371/journal.pcbi.1002037. View

10.

Kim M, Kim Y . Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr Res Pract. 2010; 4(3):191-5. PMC: 2895698. DOI: 10.4162/nrp.2010.4.3.191. View

11.

Yoshioka T, Fujii E, Endo M, Wada K, Tokunaga Y, Shiba N . Antiinflammatory potency of dehydrocurdione, a zedoary-derived sesquiterpene. Inflamm Res. 1999; 47(12):476-81. DOI: 10.1007/s000110050361. View

12.

Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y . A novel chemometric method for the prediction of human oral bioavailability. Int J Mol Sci. 2012; 13(6):6964-6982. PMC: 3397506. DOI: 10.3390/ijms13066964. View

13.

Wang Y, Liu Z, Li C, Li D, Ouyang Y, Yu J . Drug target prediction based on the herbs components: the study on the multitargets pharmacological mechanism of qishenkeli acting on the coronary heart disease. Evid Based Complement Alternat Med. 2012; 2012:698531. PMC: 3310183. DOI: 10.1155/2012/698531. View

14.

Murthy D, Attri K, Gokhale R . Network, nodes and nexus: systems approach to multitarget therapeutics. Curr Opin Biotechnol. 2013; 24(6):1129-36. DOI: 10.1016/j.copbio.2013.02.009. View

15.

Singh N, Guha R, Giulianotti M, Pinilla C, Houghten R, Medina-Franco J . Chemoinformatic analysis of combinatorial libraries, drugs, natural products, and molecular libraries small molecule repository. J Chem Inf Model. 2009; 49(4):1010-24. PMC: 2686115. DOI: 10.1021/ci800426u. View

16.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View

17.

Pan M, Huang T, Lin J . Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999; 27(4):486-94. View

18.

Wang X, Xu X, Tao W, Li Y, Wang Y, Yang L . A systems biology approach to uncovering pharmacological synergy in herbal medicines with applications to cardiovascular disease. Evid Based Complement Alternat Med. 2012; 2012:519031. PMC: 3518963. DOI: 10.1155/2012/519031. View

19.

Morrow J, Tian L, Zhang S . Molecular networks in drug discovery. Crit Rev Biomed Eng. 2010; 38(2):143-56. PMC: 3820486. DOI: 10.1615/critrevbiomedeng.v38.i2.30. View

20.

Wist A, Berger S, Iyengar R . Systems pharmacology and genome medicine: a future perspective. Genome Med. 2009; 1(1):11. PMC: 2651594. DOI: 10.1186/gm11. View