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      Comparing the antidiabetic effects and chemical profiles of raw and fermented Chinese Ge-Gen-Qin-Lian decoction by integrating untargeted metabolomics and targeted analysis

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          Abstract

          Background

          Microbial fermentation has been widely applied in traditional Chinese medicine (TCM) for thousands of years in China. Various beneficial effects of fermentation for applications in TCM or herbals have been reported, such as enhanced anti-ovarian cancer, antioxidative activity, and neuroprotective effects. Ge-Gen-Qin-Lian decoction (GQD), a classic TCM formula, has been used to treat type 2 diabetes mellitus in China. In this study, GQD was fermented with Saccharomyces cerevisiae, and the antidiabetic activities and overall chemical profiles of raw and fermented GQD (FGQD) were systematically compared.

          Methods

          First, the antidiabetic effects of GQD and FGQD on high-fat diet and streptozotocin (STZ)-induced diabetic rats were compared. Then, high-performance liquid chromatography Q Exactive MS was applied for rapid characterization of the chemical components of GQD. Additionally, we proposed an integrated chromatographic technique based untargeted metabolomics identifying differential chemical markers between GQD and FGQD and targeted analysis determining the fermenting-induced quantitative variation tendencies of chemical marker strategy for overall chemical profiling of raw and fermented GQD.

          Results

          Both GQD and FGQD displayed effects against HFD and STZ-induced diabetes, and FGQD showed a better recovery trend associated with profound changes in the serum lipoprotein profile and body weight gain. In addition, 133 compounds were characterized from GQD. It was demonstrated that the integrated strategy holistically illuminated 30 chemical markers contributed to the separation of GQD and FGQD, and further elucidated the fermenting-induced chemical transformation mechanisms and inherent chemical connections of secondary metabolites. Although there were no new secondary metabolites in FGQD compared with GQD, the amounts of secondary metabolites, which were mostly deglycosylated, were redistributed in FGQD.

          Conclusion

          The anti-diabetic activities of GQD could be improved by applying fermentation technology. Moreover, the proposed strategy could serve as a powerful tool for systematically exploring the chemical profiles of raw and fermented formulas.

          Electronic supplementary material

          The online version of this article (10.1186/s13020-018-0208-7) contains supplementary material, which is available to authorized users.

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          Most cited references44

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          Antidiabetic effects of fermented soybean products on type 2 diabetes.

          Historically, the incidence of type 2 diabetes has been lower in Asian populations compared with those in Western countries. One possible reason for the lower incidence among Asians is that they consume fermented soybean products, which are unique to the traditional Asian diet. Some have hypothesized that dietary phytoestrogens and soy peptides in fermented soybean foods consumed in traditional Asian diets may help prevent and slow the progression of type 2 diabetes. This review evaluates the existing evidence from animal studies and clinical and epidemiologic investigations on fermented soybeans in the prevention and treatment of type 2 diabetes. Nutritional studies performed in animals and intervention studies with humans suggest that the ingestion of soy protein with isoflavones improves glucose control and reduces insulin resistance. Korean fermented soybean products such as doenjang, kochujang, and chungkookjang contain alterations in the structures and content of isoflavonoids and small bioactive peptides, which are produced during fermentation. Several studies revealed improvements in insulin resistance and insulin secretion with the consumption of these fermented products. Therefore, fermented soybean products may help prevent or attenuate the progression of type 2 diabetes. Although the lack of human intervention trials does not permit definitive conclusions, the evidence does suggest that fermented soy products may be better for preventing or delaying the progression of type 2 diabetes compared with nonfermented soybeans. 2010 Elsevier Inc. All rights reserved.
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            Method validation strategies involved in non-targeted metabolomics.

            Non-targeted metabolomics is the hypothesis generating, global unbiased analysis of all the small-molecule metabolites present within a biological system, under a given set of conditions. It includes several common steps such as selection of biological samples, sample pre-treatment, analytical conditions set-up, acquiring data, data analysis by chemometrics, database search and biological interpretation. Non-targeted metabolomics offers the potential for a holistic approach in the area of biomedical research in order to improve disease diagnosis and to understand its pathological mechanisms. Various analytical methods have been developed based on nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) coupled with different separation techniques. The key points in any analytical method development are the validation of every step to get a reliable and reproducible result and non-targeted metabolomics is not beyond this criteria, although analytical challenges are completely new and different to target methods. This review paper will describe the available validation strategies that are being used and as well will recommend some steps to consider during a non-targeted metabolomics analytical method development. Copyright © 2014 Elsevier B.V. All rights reserved.
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              Identification of novel anti-inflammatory agents from Ayurvedic medicine for prevention of chronic diseases: "reverse pharmacology" and "bedside to bench" approach.

              Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.
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                Author and article information

                Contributors
                yanyan520@sxu.edu.cn
                duchenxi_2001@163.com
                lizhenyu@sxu.edu.cn
                2862613255@qq.com
                li_jin2006@126.com
                1091737660@qq.com
                774194125@qq.com
                +86-351-7018379 , qinxm@sxu.edu.cn
                +86-351-3179978 , sxhpe@163.com
                Journal
                Chin Med
                Chin Med
                Chinese Medicine
                BioMed Central (London )
                1749-8546
                26 October 2018
                26 October 2018
                2018
                : 13
                : 54
                Affiliations
                [1 ]ISNI 0000 0004 1760 2008, GRID grid.163032.5, Modern Research Center for Traditional Chinese Medicine of Shanxi University, ; No. 92, Wucheng Road, Taiyuan, 030006 Shanxi China
                [2 ]ISNI 0000 0004 1760 2008, GRID grid.163032.5, School of Traditional Chinese Materia Medica, , Shanxi University of Chinese Medicine, ; No. 121, Daxue Street, Taiyuan, 030619 Shanxi China
                [3 ]ISNI 0000 0004 1760 2008, GRID grid.163032.5, College of Chemistry and Chemical Engineering of Shanxi University, ; No. 92, Wucheng Road, Taiyuan, 030006 Shanxi China
                Author information
                http://orcid.org/0000-0003-2120-4662
                Article
                208
                10.1186/s13020-018-0208-7
                6204051
                30386417
                abc2a0a7-dcdd-4c5e-8cf9-258f5927e129
                © 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
                : 25 July 2018
                : 24 September 2018
                Funding
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 81273659
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Complementary & Alternative medicine
                ge-gen-qin-lian decoction,fermentation,untargeted metabolomics,targeted analysis,antidiabetic effects

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