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      UPLC-HRMS-Based Plasma Metabolomic Profiling of Novel Biomarkers by Treatment with KDZI in Cerebral Ischemia Reperfusion Rats

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          Abstract

          Kudiezi injection (KDZI), also known as Diemailing injection, is a traditional Chinese medicine injection of the composite plant Ixeris sonchifolia Hance (also known as Kudiezi), and has been widely used to treat coronary heart disease, angina pectoris, and cerebral infarction, but its pharmacological mechanisms remain unclear. This study is designed to explore the effects of KDZI on middle cerebral artery occlusion and reperfusion (MCAO/R) rats, and to identify metabolic features of cerebral ischemia reperfusion by using a nontargeted metabolic profiling method based on ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). In this process, 32 potential biomarkers were found in plasma. KDZI significantly upregulated the levels of taurochenodesoxycholic acid, leucine, l-phenylalanine, l-tryptophan, arachidonic acid (ARA), and phosphatidyl ethanolamines (PE), phosphatidyl cholines (PC) and downregulated the levels of l-valine and 5-hydroxyindole-3-acetic acid (5-HIAA) in plasma. The results indicated that the mechanisms of KDZI on MCAO/R were related to the mechanisms of amino acid and lipid metabolism.

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          Metabonomics: a platform for studying drug toxicity and gene function.

          Jeremy Nicholson, John C Connelly, John C. Lindon … (2002)
          The later that a molecule or molecular class is lost from the drug development pipeline, the higher the financial cost. Minimizing attrition is therefore one of the most important aims of a pharmaceutical discovery programme. Novel technologies that increase the probability of making the right choice early save resources, and promote safety, efficacy and profitability. Metabonomics is a systems approach for studying in vivo metabolic profiles, which promises to provide information on drug toxicity, disease processes and gene function at several stages in the discovery-and-development process.
          Article 0 comments Cited 309 times – based on 0 reviews     Review now
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            Global metabolic profiling of animal and human tissues via UPLC-MS.

            Elizabeth J Want, Perrine Masson, Filippos Michopoulos … (2013)
            Obtaining comprehensive, untargeted metabolic profiles for complex solid samples, e.g., animal tissues, requires sample preparation and access to information-rich analytical methodologies such as mass spectrometry (MS). Here we describe a practical two-step process for tissue samples that is based on extraction into 'aqueous' and 'organic' phases for polar and nonpolar metabolites. Separation methods such as ultraperformance liquid chromatography (UPLC) in combination with MS are needed to obtain sufficient resolution to create diagnostic metabolic profiles and identify candidate biomarkers. We provide detailed protocols for sample preparation, chromatographic procedures, multivariate analysis and metabolite identification via tandem MS (MS/MS) techniques and high-resolution MS. By using these optimized approaches, analysis of a set of samples using a 96-well plate format would take ~48 h: 1 h for system setup, 8-10 h for sample preparation, 34 h for UPLC-MS analysis and 2-3 h for preliminary/exploratory data processing, representing a robust method for untargeted metabolic screening of tissue samples.
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              Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics.

              Pei-qiang Huang, Yexiong Tan, Peiyuan Yin … (2013)
              Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and β-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein.
              Article 0 comments Cited 174 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 30 May 2018
                Publication date Collection: June 2018
                Volume: 23
                Issue: 6
                Electronic Location Identifier: 1315
                Affiliations
                [1 ]Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; wangcg1119@ 123456126.com
                [2 ]School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; liuchenyue633@ 123456163.com (C.L.); weme9916@ 123456163.com (M.W.); maquantao@ 123456bucm.edu.cn (Q.M.); liyaqi@ 123456bucm.edu.com (Y.L.)
                [3 ]School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
                Author notes
                [* ]Correspondence: wangting1973@ 123456sina.com (T.W.); zhaobs1973@ 123456163.com (B.Z.); Tel./Fax: +86-010-64286203 (T.W.); +86-010-64286894 (B.Z.)
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-2711-1144
                Article
                Publisher ID: molecules-23-01315
                DOI: 10.3390/molecules23061315
                PMC ID: 6099697
                PubMed ID: 29849010
                SO-VID: 2b1c4a3b-4d34-44dc-92f1-a7c6452116b1
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 May 2018
                Date accepted : 24 May 2018
                Categories
                Subject: Article

                Keywords: kudiezi injection,uplc-hrms,middle cerebral artery occlusion and reperfusion
                Data availability:
                Keywords: kudiezi injection, uplc-hrms, middle cerebral artery occlusion and reperfusion

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