Identifying potential therapeutic targets of a natural product Jujuboside B for insomnia through network pharmacology.

Authors

  • Hongwei Du Heilongjiang Academy of Traditional Chinese medicine, Sanfu Road 142, Xiangfang District, Harbin, Heilongjiang Province
  • Xinlei Zhao Heilongjiang Province Hospital, Zhongshan Road, Xiangfang District, Harbin 150036, Heilongjiang Province
  • Aihua Zhang Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040

DOI:

https://doi.org/10.14719/pst.2014.1.2.26

Keywords:

Interaction network, Network pharmacology, Jujuboside B, Insomnia, Targets, Differentially expressed genes

Abstract

Knowledge of the interactome improves the understanding of disease metabolism. Biological information about interactions among genes and their protein products, computationally extracted in the context of SysBiomics, can hint at molecular causes of diseases, be essential for understanding biological systems, and provide clues for new therapeutic approaches. Quick and efficient access to this data have become critical issues for biologists. We have implemented a computational platform that integrates pathway, protein–protein interaction, differentially expressed genome and literature mining data to result in comprehensive networks for insomnia and intervention effects of Jujuboside B (JuB). The interaction data were imported into Cytoscape software, a popular bioinformatics package for biological network visualization and data integration, for screening the central nodes of the network, exploiting functional study of the central node genes, exploring the mechanism of insomnia. Results showed that seven differentially expressed genes confirmed by Cytoscape as the central nodes of the network in insomnia had interactions, forming a complicated interaction network (77 nodes, 96 edges). Among gene nodes, HBA1, LEP, MAOA, PRNP, GHRL, CLOCK and SLC6A4 were verified as the genes with maximal differential expressions. Of note, we further observed that the HBA1, LEP, SLC6A4 and MAOA were JuB target genes. The interaction network of the differentially expressed genes, especially the central nodes of this network, can provide clues to the insomnia, early diagnosis and molecular targeted therapy. Our findings demonstrate that the integration of interaction network in genomic space can not only speed the genome-wide identification of drug targets but also find new applications for the existing drugs.

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References

Beland, S. G., Preville, M., Dubois, M. F., Lorrain, D., Grenier, S., Voyer, P., Perodeau, G., & Moride, Y. (2010). Benzodiazepine use and quality of sleep in the community-dwelling elderly population. Aging & Mental Health, 14, 843-850. [PubMed: 20658372] doi:10.1080/13607861003781833

Burga, A., Casanueva, M. O., & Lehner, B. (2011). Predicting mutation outcome from early stochastic variation in genetic interaction partners. Nature, 480, 250-253. [PubMed: 22158248] doi:10.1038/nature10665

Cline, M. S., Smoot, M., Cerami, E., Kuchinsky, A., Landys, N., Workman, C., … Bader, G. D. (2007). Integration of biological networks and gene expression data using Cytoscape. Nature Protocols, 2, 2366-2382. [PubMed: 17947979] doi:10.1038/nprot.2007.324

Fang, X. Sh., Hao, J. F., Zhou, H. Y., Zhu, L. X., Wang, J. H., & Song, F. Q. (2010). Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations. Phytomedicine. 17, 75-80. [PubMed: 19682877] doi:10.1016/j.phymed.2009.07.004

Gilchrist, M., Thorsson, V., Li, B., Rust, A. G., Korb, M., Roach, J. C., … Aderem, A. (2006). Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature, 441, 173-178. [PubMed: 16688168] doi:10.1038/nature04768

Gu, J., Chen, Y., Li, S., & Li, Y. (2010). Identification of responsive gene modules by network-based gene clustering and extending: application to inflammation and angiogenesis. BMC Systems Biology, 4, 47. [PubMed: 20406493] doi:10.1186/1752-0509-4-47

Hopkins, A. L. (2008). Network pharmacology: the next paradigm in drug discovery. Nature Chemical Biology, 4, 682-690. [PubMed: 18936753] doi:10.1038/nchembio.118

Janga, S. C., & Tzakos, A. (2009). Structure and organization of drug-target networks: insights from genomic approaches for drug discovery. Molecular Biosystematics, 5, 1536-1548. [PubMed: 19763339]

Ma, T., Tan, C., Zhang, H., Wang, M., Ding, W., & Li, S. (2010). Bridging the gap between traditional Chinese medicine and systems biology: the connection of Cold Syndrome and NEI network. Molecular Biosystematics, 6, 613-619. [PubMed: 20237638] doi:10.1039/b914024g

Mahowald, M. W. & Schenck, C. H. (2005). Insights from studying human sleep disorders. Nature, 437, 1279-1285 doi:10.1038/nature04287 [PubMed: 16251953]

Mestres, J., Gregori-Puigjané, E., Valverde, S., & Solé, R. V. (2009). The topology of drug-target interaction networks: implicit dependence on drug properties and target families. Molecular Biosystematics, 5, 1051-1057. [PubMed: 19668871]

Raman, K., Vashisht, R., & Chandra, N. (2009). Strategies for efficient disruption of metabolism in Mycobacterium tuberculosis from network analysis. Molecular Biosystematics, 5, 1740-1751. [PubMed: 19593474] doi:10.1039/b905817f

Richey, S. M., & Krystal, A. D. (2011). Pharmacological advances in the treatment of insomnia. Current Pharmaceutical Design, 17, 1471-1475. [PubMed: 21476952] doi:10.2174/138161211796197052

Sarris, J., & Byrne, G. J. (2011). A systematic review of insomnia and complementary medicine. Sleep Medicine Reviews, 15, 99-106. [PubMed: 20965131] doi:10.1016/j.smrv.2010.04.001

Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., … Ideker, T. (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498-504 doi:10.1101/gr.1239303 [PubMed: 14597658]

Shimomura, K., Lowrey, P. L., Vitaterna, M. H., Buhr, E. D., Kumar, V., Hanna, P., … Takahashi, J. S. (2010). Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway. Proceedings of the National Academy of Sciences of the United States of America, 107, 8399-8403. [PubMed: 20404168] doi:10.1073/pnas.1004368107

Silva-Rocha, R., & de Lorenzo, V. (2011). Implementing an OR-NOT (ORN) logic gate with components of the SOS regulatory network of Escherichia coli. Molecular Biosystematics, 7, 2389-2396. [PubMed: 21584342] doi:10.1039/c1mb05094j

Tamble, C. M., St Onge, R. P., Giaever, G., Nislow, C., Williams, A. G., Stuart, J, M., & Lokey, R. S. (2011). The synthetic genetic interaction network reveals small molecules that target specific pathways in Sacchromyces cerevisiae. Molecular Biosystematics, 7, 2019-2030. [PubMed: 21487606] doi:10.1039/c0mb00298d

Telesco, S. E., Shih, A. J., Jia, F., & Radhakrishnan, R. (2011). A multiscale modeling approach to investigate molecular mechanisms of pseudokinase activation and drug resistance in the HER3/ErbB3 receptor tyrosine kinase signaling network. Molecular Biosystematics, 7, 2066-2080. [PubMed: 21509365] doi:10.1039/c0mb00345j

Vecsey, C. G., Baillie, G. S., Jaganath, D., Havekes, R., Daniels, A., Wimmer, M., … Abel, T. (2009). Sleep deprivation impairs cAMP signalling in the hippocampus. Nature, 461, 1122-1125. [PubMed: 19847264] doi:10.1038/nature08488

Wang, L., Zhou, G. B., Liu, P., Song, J. H., Liang, Y., Yan, X. J., … Chen, Z. (2008). Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America. 105, 4826-4831. [PubMed: 18344322] doi:10.1073/pnas.0712365105

Wu, X., Jiang, R., Zhang, M. Q., & Li, S. (2008). Network-based global inference of human disease genes. Molecular Systems Biology. 4, 189. [PubMed: 18463613] doi:10.1038/msb.2008.27

Yang, B., Zhang, A., Sun, H., Dong, W., Yan, G., Li, T., & Wang, X. (2012). Metabolomic study of insomnia and intervention effects of Suanzaoren decoction using ultra-performance liquid-chromatography/electrospray-ionization synapt high-definition mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 58, 113-124. [PubMed: 22019702] doi:10.1016/j.jpba.2011.09.033

Yao, X., Hao, H., Li, Y., & Li, S. (2011). Modularity-based credible prediction of disease genes and detection of disease subtypes on the phenotype-gene heterogeneous network. BMC Systems Biology, 5, 79. [PubMed: 21599985] doi:10.1186/1752-0509-5-79

Zhang, A., Sun, H., Yang, B., & Wang, X. (2012). Predicting new molecular targets for rhein using network pharmacology. BMC Systems Biology, 6, 20. PMID: 22433437 doi:10.1186/1752-0509-6-20

Zhang, B., Shi, Z., Duncan, D. T., Prodduturi, N., Marnett, L. J., & Liebler, D. C. (2011). Relating protein adduction to gene expression changes: a systems approach. Molecular Biosystematics, 7, 2118-2127. [PubMed: 21594272] doi:10.1039/c1mb05014a

Zhao, J., Li, S. P., Yang, F. Q., Li, P., & Wang, Y. T. (2006). Simultaneous determination of saponins and fatty acids in Ziziphus jujuba (Suanzaoren) by high performance liquid chromatography-evaporative light scattering detection and pressurized liquid extraction. Journal of Chromatography A, 1108, 188-194. [PubMed:16458908] doi:10.1016/j.chroma.2005.12.104

Zou, J., Luo, S. D., Wei, Y. Q., & Yang, S. Y. (2011). Integrated computational model of cell cycle and checkpoint reveals different essential roles of Aurora-A and Plk1 in mitotic entry. Molecular Biosystematics, 7, 169-179. [PubMed: 20978655] doi:10.1039/c0mb00004c

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Published

05-05-2014

How to Cite

1.
Du H, Zhao X, Zhang A. Identifying potential therapeutic targets of a natural product Jujuboside B for insomnia through network pharmacology. Plant Sci. Today [Internet]. 2014 May 5 [cited 2024 Nov. 23];1(2):69-7. Available from: https://horizonepublishing.com/journals/index.php/PST/article/view/26

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