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Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits.
- Source :
-
Journal of ethnopharmacology [J Ethnopharmacol] 2014 Mar 14; Vol. 152 (2), pp. 272-82. Date of Electronic Publication: 2014 Jan 18. - Publication Year :
- 2014
-
Abstract
- Ethnopharmacological Relevance: In the recent years, the international community has attached increasing importance to possible toxicity associated with Traditional Chinese Medicine (TCM). And hepatotoxicity is one of the major concerns, a fundamental pathological process induced by toxicant. This paper is in an attempt to identify the hepatotoxic components in Xanthium strumarium L. fruits (XSF) and interpret the toxicological mechanism induced by XSF.<br />Materials and Methods: XSF extract was prepared and seven characteristic components were isolated and identiļ¬ed in XSF water extracts. We evaluated their hepatotoxicity effect on cell proliferation and lactate dehydrogenase (LDH) activity in L-02 and BRL liver cell line. An integrated metabonomics study using high-resolution (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy combined with multivariate statistical analysis was undertake to elucidate the hepatotoxicity mechanism induced in rats by XSF. The urine and serum metabolites were measured after treatment of rats with XSF (7.5, 15.0 and 30.0 g/kg/day) for 5 days.<br />Results: The results showed that atractyloside, carboxyatractyloside, 4'-desulphate-atractyloside and XSF induced significant cytotoxic effects in both L-02 and BRL liver cell lines, indicating that atractyloside, carboxyatractyloside, and 4'-desulphate-atractyloside were the toxic components of XSF. When rats were treated with XSF at 30.0 g/kg the hepatotoxicity was reflected in the changes observed in serum biochemical profiles and by the histopathological examination of the liver. The levels of VLDL/LDL, 3-HB, lactate, acetate, acetone and glutamate in serum were increased in this group, while d-glucose, choline and valine were decreased. The elevation in the levels of succinate, citrate, 2-oxo-glutamate, glycine, 3-HB, acetate, lactate, hippurate, dimethylglycine, methylamine, dimethylamine, phenylalanine and tryptophan was observed in urine, in contrast a reduction in the intensities of taurine, d-glucose, N-acetyl-glucoprotein and trimethylamine-N-oxide (TMAO) was observed.<br />Conclusions: The results demonstrate that the major hepatotoxicity constituents are atractyloside, carboxyatractyloside and 4'-desulphate-atractyloside, and the hepatotoxicity of XSF involves mitochondrial inability, fatty acid metabolism, and some amino acids metabolism. This integrated (1)H NMR -based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of hepatotoxicity induced by XSF, and permits a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Animals
Cell Line
Chemical and Drug Induced Liver Injury pathology
Dose-Response Relationship, Drug
Fruit
Humans
Liver pathology
Magnetic Resonance Spectroscopy
Male
Medicine, Chinese Traditional adverse effects
Metabolomics
Multivariate Analysis
Plant Extracts administration & dosage
Plant Extracts chemistry
Rats
Rats, Wistar
Chemical and Drug Induced Liver Injury etiology
Liver drug effects
Plant Extracts toxicity
Xanthium chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7573
- Volume :
- 152
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 24447814
- Full Text :
- https://doi.org/10.1016/j.jep.2013.12.024