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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

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      A network pharmacology approach to determine the synergetic mechanisms of herb couple for treating rheumatic arthritis

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Purpose

          The purpose of this study was to investigate the therapeutic mechanism(s) of Clematis chinensis Osbeck/ Notopterygium incisum K.C. Ting ex H.T (CN).

          Methods

          A network pharmacology approach integrating prediction of ingredients, target exploration, network construction, module partition and pathway analysis was used.

          Results

          This approach successfully helped to identify 12 active ingredients of CN, interacting with 13 key targets (Akt1, STAT3, TNFsf13, TP53, EPHB2, IL-10, IL-6, TNF, MAPK8, IL-8, RELA, ROS1 and STAT4). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that CN-regulated pathways were mainly classified into signal transduction and immune system.

          Conclusion

          The present work may help to illustrate the mechanism(s) of action of CN, and it may provide a better understanding of antirheumatic effects.

          Most cited references34

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          Angiogenesis in life, disease and medicine.

          Peter Carmeliet (2005)
          The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.
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            JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

            Shubhasree Banerjee, Ann Biehl, Massimo Gadina … (2017)
            The Janus kinase/signal transduction and activator of transcription (JAK–STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK–STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK–STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK–STAT signaling blockade.
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              The pathogenic role of angiogenesis in rheumatoid arthritis.

              Hatem A Elshabrawy, Zhenlong Chen, Michael Volin … (2015)
              Angiogenesis is the formation of new capillaries from pre-existing vasculature, which plays a critical role in the pathogenesis of several inflammatory autoimmune diseases such as rheumatoid arthritis (RA), spondyloarthropathies, psoriasis, systemic lupus erythematosus, systemic sclerosis, and atherosclerosis. In RA, excessive migration of circulating leukocytes into the inflamed joint necessitates formation of new blood vessels to provide nutrients and oxygen to the hypertrophic joint. The dominance of the pro-angiogenic factors over the endogenous angiostatic mediators triggers angiogenesis. In this review article, we highlight the underlying mechanisms by which cells present in the RA synovial tissue are modulated to secrete pro-angiogenic factors. We focus on the significance of pro-angiogenic factors such as growth factors, hypoxia-inducible factors, cytokines, chemokines, matrix metalloproteinases, and adhesion molecules on RA pathogenesis. As pro-angiogenic factors are primarily produced from RA synovial tissue macrophages and fibroblasts, we emphasize the key role of RA synovial tissue lining layer in maintaining synovitis through neovascularization. Lastly, we summarize the specific approaches utilized to target angiogenesis. We conclude that the formation of new blood vessels plays an indispensable role in RA progression. However, since the function of several pro-angiogenic mediators is cross regulated, discovering novel approaches to target multiple cascades or selecting an upstream cascade that impairs the activity of a number of pro-angiogenic factors may provide a promising strategy for RA therapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): Drug Design, Development and Therapy
                Title: Drug Design, Development and Therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1177-8881
                Publication date Collection: 2018
                Publication date (Electronic): 24 April 2018
                Volume: 12
                Pages: 967-979
                Affiliations
                [1 ]State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China
                [2 ]Orthopedics Department, Shandong Provincial Traditional Chinese Medical Hospital, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China
                [3 ]Center for Drug Safety Evaluation and Research, Zhejiang University, Hangzhou, People’s Republic of China
                [4 ]School of Pharmacy, Xinjiang Medical University, Urumqi, People’s Republic of China
                Author notes
                Correspondence: Fei Li; Ping Li, State Key Laboratory of Natural Medicines, China Pharmaceutical University, No 24 Tongjia Lane, Nanjing 210009, People’s Republic of China, Tel/fax +86 25 8327 1382, Email lifeicpu@ 123456163.com ; liping2004@ 123456126.com
                Article
                Publisher ID: dddt-12-967
                DOI: 10.2147/DDDT.S161904
                PMC ID: 5923250
                PubMed ID: 29731604
                SO-VID: cbc1543c-7a51-48cd-8db2-e712ebd9a954
                Copyright © © 2018 Xu et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: targets prediction,pathways analysis,action mechanism,clematis chinensis osbeck,notopterygium incisum k.c. ting ex h.t. chang
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: targets prediction, pathways analysis, action mechanism, clematis chinensis osbeck, notopterygium incisum k.c. ting ex h.t. chang

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