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      A Network Study of Chinese Medicine Xuesaitong Injection to Elucidate a Complex Mode of Action with Multicompound, Multitarget, and Multipathway

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          Abstract

          Chinese medicine has evolved from thousands of years of empirical applications and experiences of combating diseases. It has become widely recognized that the Chinese medicine acts through complex mechanisms featured as multicompound, multitarget and multipathway. However, there is still a lack of systematic experimental studies to elucidate the mechanisms of Chinese medicine. In this study, the differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with Xuesaitong Injection (XST), a Chinese medicine consisting of the total saponins from Panax notoginseng (Burk.) F. H. Chen (Chinese Sanqi). A network-based approach was developed to combine DEGs related to cardiovascular diseases (CVD) with lines of evidence from the literature mining to investigate the mechanism of action (MOA) of XST on antimyocardial infarction. A compound-target-pathway network of XST was constructed by connecting compounds to DEGs validated with literature lines of evidence and the pathways that are functionally enriched. Seventy potential targets of XST were identified in this study, of which 32 were experimentally validated either by our in vitro assays or by CVD-related literatures. This study provided for the first time a network view on the complex MOA of antimyocardial infarction through multiple targets and pathways.

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          Most cited references 46

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          Autocrine VEGF signaling is required for vascular homeostasis.

          Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Here we show that in the absence of any pathological insult, autocrine VEGF is required for the homeostasis of blood vessels in the adult. Genetic deletion of vegf specifically in the endothelial lineage leads to progressive endothelial degeneration and sudden death in 55% of mutant mice by 25 weeks of age. The phenotype is manifested without detectable changes in the total levels of VEGF mRNA or protein, indicating that paracrine VEGF could not compensate for the absence of endothelial VEGF. Furthermore, wild-type, but not VEGF null, endothelial cells showed phosphorylation of VEGFR2 in the absence of exogenous VEGF. Activation of the receptor in wild-type cells was suppressed by small molecule antagonists but not by extracellular blockade of VEGF. These results reveal a cell-autonomous VEGF signaling pathway that holds significance for vascular homeostasis but is dispensable for the angiogenic cascade.
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            TCM: Made in China.

             Felix Cheung (2011)
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              Molecular networks for the study of TCM pharmacology.

              To target complex, multi-factorial diseases more effectively, there has been an emerging trend of multi-target drug development based on network biology, as well as an increasing interest in traditional Chinese medicine (TCM) that applies a more holistic treatment to diseases. Thousands of years' clinic practices in TCM have accumulated a considerable number of formulae that exhibit reliable in vivo efficacy and safety. However, the molecular mechanisms responsible for their therapeutic effectiveness are still unclear. The development of network-based systems biology has provided considerable support for the understanding of the holistic, complementary and synergic essence of TCM in the context of molecular networks. This review introduces available sources and methods that could be utilized for the network-based study of TCM pharmacology, proposes a workflow for network-based TCM pharmacology study, and presents two case studies on applying these sources and methods to understand the mode of action of TCM recipes.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2013
                24 August 2013
                24 August 2013
                : 2013
                Affiliations
                1Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
                2State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
                3College of Preclinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
                Author notes
                *Xiaohui Fan: fanxh@ 123456zju.edu.cn and

                Academic Editor: Ke Liu

                Article
                10.1155/2013/652373
                3766588
                24058375
                17a72f0d-e07f-4da3-b3fe-e91386d154fc
                Copyright © 2013 Linli Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: http://dx.doi.org/10.13039/501100001809 National Natural Science Foundation of China
                Award ID: 81273991
                Categories
                Research Article

                Complementary & Alternative medicine

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