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System-level multi-target drug discovery from natural products with applications to cardiovascular diseases

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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.

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Acknowledgments

We would like to express our sincere gratitude to Editor in Chief Guillermo A. Morales for assistance with the English correction of the manuscript. This work was supported by Grants from Northwest A & F University, National Natural Science Foundation of China (31170796 and 81373892). And it also was supported in part by China Academy of Chinese Medical Sciences (ZZ0608).

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Authors and Affiliations

  1. Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China

    Chunli Zheng, Jinan Wang, Chao Huang & Yonghua Wang

  2. College of Life Science, Northwest University, Xi’an, Shaanxi, China

    Jianling Liu & Mengjie Pei

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  1. Chunli Zheng
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  2. Jinan Wang
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  3. Jianling Liu
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Correspondence to Yonghua Wang.

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Chunli Zheng and Jinan Wang have contributed equally to this study.

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Zheng, C., Wang, J., Liu, J. et al. System-level multi-target drug discovery from natural products with applications to cardiovascular diseases. Mol Divers 18, 621–635 (2014). https://doi.org/10.1007/s11030-014-9521-y

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