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      Recent Advance in Applications of Proteomics Technologies on Traditional Chinese Medicine Research

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          Abstract

          Proteomics technology, a major component of system biology, has gained comprehensive attention in the area of medical diagnosis, drug development, and mechanism research. On the holistic and systemic theory, proteomics has a convergence with traditional Chinese medicine (TCM). In this review, we discussed the applications of proteomic technologies in diseases-TCM syndrome combination researches. We also introduced the proteomic studies on the in vivo and in vitro effects and underlying mechanisms of TCM treatments using Chinese herbal medicine (CHM), Chinese herbal formula (CHF), and acupuncture. Furthermore, the combined studies of proteomics with other “-omics” technologies in TCM were also discussed. In summary, this report presents an overview of the recent advances in the application of proteomic technologies in TCM studies and sheds a light on the future global and further research on TCM.

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          Most cited references81

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          Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies.

          To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.
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            The effects of the Chinese medicine ZiBu PiYin recipe on the hippocampus in a rat model of diabetes-associated cognitive decline: a proteomic analysis.

            Increasing evidence suggests that diabetes is associated with an enhanced risk of cognitive decline. The precise mechanisms underlying diabetes-associated cognitive decline (DACD) remain unclear. Here we investigated the molecular changes associated with DACD using a comparative proteomics study of hippocampus in a rat model of type 2 diabetes. In addition, we tested the effects of the Chinese medicine ZiBu PiYin recipe (ZBPYR) on DACD. The hippocampus was dissected from control, diabetic and diabetic rats treated with ZBPYR (DM/ZBPYR). Soluble proteins were separated using fluorescence-based difference gel electrophoresis. Protein spots were visualised with fluorescent dyes and spot density was compared between each pair of groups. Proteins of interest were identified using mass spectrometry. Proteins of specific interest were also tested by western blot and real-time PCR analysis. We found 13 spots that were altered between control and diabetes groups, and 12 spots that were changed between diabetes and DM/ZBPYR groups. The identities of nine proteins were determined by mass spectrometry. The identified proteins were largely involved in energy metabolism, cytoskeleton regulation and oxidative stress. The protein alterations observed in the diabetes group were ameliorated to varying degrees following ZBPYR treatment. The protein changes identified in hippocampus from a rat model of type 2 diabetes suggest that specific cellular alterations contribute to DACD. The Chinese medicine ZBPYR was found to affect multiple targets and partially repaired the original cellular balance. This study may provide important insights into the molecular events underlying DACD and allow the identification of novel therapeutic targets.
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              Functional proteomic and structural insights into molecular targets related to the growth inhibitory effect of tanshinone IIA on HeLa cells.

              Certain antitumor agents have recently been extracted from the roots of Salvia miltiorrhiza Bunge. The diterpene derivative, tanshinone IIA, possesses cytotoxic activity against several human carcinoma cell lines. It also inhibits invasion and metastasis of cancer cells. In the present study, we isolated tanshinone IIA from S. miltiorrhiza, and it exhibited strong growth inhibition against human cervical cancer cells in dose- and time-dependent manners with a 50% cell growth inhibition value of 2.5 microg/mL (8.49 microM). Flow cytometric analysis of cell cycle progression revealed that G(2)/M arrest was initiated after a 24 h exposure to the drug. It also resulted in DNA fragmentation and degradation of poly (ADP-ribose) polymerase indicating that tanshinone IIA may be a potential antitumor agent. Furthermore, we performed a comprehensive proteomic analysis to survey global protein changes induced by tanshinone IIA treatment on HeLa cells. Significant changes in the levels of cytoskeleton proteins as well as stress-associated proteins were observed. Immunoblot analysis and immunofluorescence staining were used to confirm the levels of protein expression. Overexpression of the vimentin rescued these tanshinone IIA-induced events. Computational docking methods indicated that tanshinone IIA could stably bind to the beta-subunit of the microtubule protein. An interaction network analysis of these 12 proteins using MetaCore software suggested that tanshinone IIA treatment regulated the expressions of proteins involved in apoptotic processes, spindle assembly, and p53 activation, including vimentin, Maspin, alpha- and beta-tubulin, and GRP75. Taken together, our results suggest that tanshinone IIA strongly inhibited the growth of cervical cancer cells through interfering in the process of microtubule assembly, leading to G(2)/M phase arrest and sequent apoptosis. The success of this large-scale effort was assessed by a bioinformatics analysis of proteins through predictions of protein domains and possible functional roles. The possible contributions of these proteins to the cytotoxicity of tanshinone IIA provide potential opportunities for the development of cancer therapeutics.
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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
                2015
                19 October 2015
                19 October 2015
                : 2015
                : 983139
                Affiliations
                1Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
                2Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
                3Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing 210028, China
                Author notes

                Academic Editor: Klaus Heese

                Article
                10.1155/2015/983139
                4629032
                26557869
                f1f67c92-9dc9-48e9-9310-f18d324dec9a
                Copyright © 2015 Qing Ji 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.

                History
                : 29 May 2015
                : 4 August 2015
                : 4 August 2015
                Categories
                Review Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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