1. Metabolic profiling of copper-laden hepatolenticular degeneration model rats and the interventional effects of Gandou decoction using UPLC-Q-TOF/MS.
- Author
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Cheng M, Wu H, Wu H, Liu X, and Zhou A
- Subjects
- Amino Acids metabolism, Animals, Biomarkers blood, Chromatography, High Pressure Liquid instrumentation, Chromatography, High Pressure Liquid methods, Copper Sulfate toxicity, Disease Models, Animal, Drugs, Chinese Herbal therapeutic use, Glucose metabolism, Hepatolenticular Degeneration chemically induced, Hepatolenticular Degeneration drug therapy, Hepatolenticular Degeneration pathology, Humans, Lipid Metabolism drug effects, Liver metabolism, Liver pathology, Male, Metabolomics instrumentation, Metabolomics methods, Multivariate Analysis, Principal Component Analysis, Rats, Tandem Mass Spectrometry instrumentation, Tandem Mass Spectrometry methods, Treatment Outcome, Drugs, Chinese Herbal pharmacology, Hepatolenticular Degeneration metabolism, Liver drug effects, Metabolic Networks and Pathways drug effects, Metabolome drug effects
- Abstract
The direct cause of hepatolenticular degeneration (HLD) is copper metabolic disorder caused by autosomal recessive inheritance. Gandou decoction (GDD), a classical traditional Chinese medicine formula, exhibits unambiguous therapeutic effect on HLD in China for decades. However, the mechanism of effect on HLD is not clear. With this purpose, the effects of copper content and histopathology inspection on the HLD rat model were investigated. Then, metabolomics study based on ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS
E ) analysis and multivariate statistical analysis was adopted to further reveal the mechanism of action of GDD against HLD. The results showed that the characteristics of liver tissues after GDD treatment were significantly reversed, close to the control group, suggesting that GDD has a therapeutic effect on HLD. Furthermore, HLD interferes with 2 metabolites of the metabolic pathway in rats. Among them, up-regulation of Lactic acid, Tryptophan, Phenylalanine, Triacylglycerol and down-regulation of Linoleic acid, Alpha Linolenic acid, Phosphatidylcholine, Taurine is particularly significant. Analysis of metabolic pathways by a unique pathway analysis revealed significant changes in several pathways including lipid metabolism, amino metabolism and glucose metabolism in HLD. This study showed that GDD could provide satisfactory therapeutic effects on HLD and metabolomics study can be utilized to further understand the molecular mechanisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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