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      Network pharmacology-based strategy to investigate pharmacological mechanisms of Zuojinwan for treatment of gastritis

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          Abstract

          Background

          Zuojinwan (ZJW), a classic herbal formula, has been extensively used to treat gastric symptoms in clinical practice in China for centuries. However, the pharmacological mechanisms of ZJW still remain vague to date.

          Methods

          In the present work, a network pharmacology-based strategy was proposed to elucidate its underlying multi-component, multi-target, and multi-pathway mode of action against gastritis. First we collected putative targets of ZJW based on TCMSP and STITCH databases, and a network containing the interactions between the putative targets of ZJW and known therapeutic targets of gastritis was built. Then four topological parameters, “degree”, “betweenness”, “closeness”, and “coreness” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Metacore database to perform a pathway enrichment analysis.

          Results

          A total of 118 nodes including 59 putative targets of ZJW were picked out as major hubs in terms of their topological importance. The results of pathway enrichment analysis indicated that putative targets of ZJW mostly participated in various pathways associated with anti-inflammation response, growth and development promotion and G-protein-coupled receptor signaling. More importantly, five putative targets of ZJW (EGFR, IL-6, IL-1β, TNF-α and MCP-1) and two known therapeutic targets of gastritis (CCKBR and IL-12β) and a link target NF-κB were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZJW acting on gastritis.

          Conclusion

          ZJW could alleviate gastritis through the molecular mechanisms predicted by network pharmacology, and this research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine (TCM) from a holistic perspective.

          Electronic supplementary material

          The online version of this article (10.1186/s12906-018-2356-9) contains supplementary material, which is available to authorized users.

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          Most cited references82

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          Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment.

          Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling done on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T-cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of six chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative reverse transcription-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be up-regulated on human CD8(+) effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8(+) effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines that produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8(+) effector T cells when implanted as xenografts in nonobese diabetic/severe combined immunodeficient mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8(+) T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of antitumor immunity.
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              High-throughput experiments are being performed at an ever-increasing rate to systematically elucidate protein-protein interaction (PPI) networks for model organisms, while the complexities of higher eukaryotes have prevented these experiments for humans. The Online Predicted Human Interaction Database (OPHID) is a web-based database of predicted interactions between human proteins. It combines the literature-derived human PPI from BIND, HPRD and MINT, with predictions made from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and Mus musculus. The 23,889 predicted interactions currently listed in OPHID are evaluated using protein domains, gene co-expression and Gene Ontology terms. OPHID can be queried using single or multiple IDs and results can be visualized using our custom graph visualization program. Freely available to academic users at http://ophid.utoronto.ca, both in tab-delimited and PSI-MI formats. Commercial users, please contact I.J. juris@ai.utoronto.ca http://ophid.utoronto.ca/supplInfo.pdf.
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                Author and article information

                Contributors
                sufei_sophie@163.com
                mhtcwang@163.com
                wangx@bucm.edu.cn
                594368334@qq.com
                811216118@qq.com
                1030492027@qq.com
                517439825@qq.com
                +86-18565780299 , yshi@bucm.edu.cn
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                1 November 2018
                1 November 2018
                2018
                : 18
                : 292
                Affiliations
                [1 ]ISNI 0000 0001 1431 9176, GRID grid.24695.3c, School of Life Sciences, Beijing University of Chinese Medicine, ; No.11 East road, North 3rd Ring Road, Beijing, 100029 China
                [2 ]ISNI 0000 0001 1431 9176, GRID grid.24695.3c, Shenzhen Hospital, Beijing University of Chinese Medicine, ; No. 1 Dayun road, Sports New City Road, Shenzhen, 518172 China
                Article
                2356
                10.1186/s12906-018-2356-9
                6211468
                30382864
                a83eb4f0-30ae-40d5-91aa-c47f906784ba
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 19 June 2018
                : 18 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004846, Beijing University of Chinese Medicine;
                Award ID: No.1000061020013
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Complementary & Alternative medicine
                zuojinwan,network pharmacology,gastritis
                Complementary & Alternative medicine
                zuojinwan, network pharmacology, gastritis

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