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Metabolic pathways involved in Xin-Ke-Shu protecting against myocardial infarction in rats using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
- Source :
-
Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2014 Mar; Vol. 90, pp. 35-44. Date of Electronic Publication: 2013 Nov 15. - Publication Year :
- 2014
-
Abstract
- Xin-Ke-Shu (XKS) is a patent drug used for coronary heart diseases in China. This study evaluated the protective effect of XKS against isoproterenol (ISO)-induced myocardial infarction (MI). For its underlying mechanism in rats with MI, a metabonomic approach was developed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS). Plasma metabolites were profiled in MI rats, pretreated orally with or without XKS. Two genres of metabolic biomarkers were used to elucidate the pharmacological action of XKS: pathological biomarkers and pharmaco biomarkers. Fifteen metabolites significantly varying between MI rats and normal rats were characterized as potential pathological biomarkers related to MI, including L-acetylcarnitine (1), L-isoleucyl-L-proline (2), tyramine (3), isobutyryl-L-carnitine (4), phytosphingosine (5), sphinganine (6), L-palmitoylcarnitine (7), lysoPC(18:0) (8), uric acid (9), L-tryptophan (10), lysoPC(18:2) (11), lysoPC(16:0) (12), docosahexaenoic acid (13), arachidonic acid (14) and linoleic acid (15). Among them, eight (1-6, 9 and 10) were first reported as pathological biomarkers related to ISO-induced MI, which mainly involved into fatty acid β-oxidation pathway, sphingolipid metabolism, proteolysis, tryptophan metabolism and purine metabolism. The metabolites significantly varying between MI rats with and without XKS pretreatment were considered as pharmaco biomarkers. A total of 17 pharmaco biomarkers were recognized, including 15 pathological biomarkers (1-15), hexanoylcarnitine (16) and tetradecanoylcarnitine (17). The results suggested that pretreatment of XKS protected metabolic perturbations in rats with MI, major via lipid pathways, amino acid metabolism and purine metabolism, which also provided a promising approach for evaluating the pharmacodynamics and mechanism of traditional Chinese medicines (TCM) formulas.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Biomarkers analysis
Cardiotonic Agents administration & dosage
Cardiotonic Agents pharmacology
Disease Models, Animal
Drugs, Chinese Herbal administration & dosage
Isoproterenol toxicity
Male
Medicine, Chinese Traditional methods
Metabolomics methods
Myocardial Infarction metabolism
Rats
Rats, Wistar
Chromatography, High Pressure Liquid methods
Drugs, Chinese Herbal pharmacology
Mass Spectrometry methods
Myocardial Infarction prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1873-264X
- Volume :
- 90
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical and biomedical analysis
- Publication Type :
- Academic Journal
- Accession number :
- 24321516
- Full Text :
- https://doi.org/10.1016/j.jpba.2013.11.008