Hepatotoxic constituents and toxicological mechanism of Xanthium strumarium L. fruits

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• 作者：Li-Ming Xue^a ; ^b ; ¹ ; Qiao-Yan Zhang^a ; ¹ ; Ping Han^c ; Yi-Ping Jiang^a ; Rong-Di Yan^d ; Yang Wang^a ; Khalid Rahman^e ; Min Jia^a ; Ting Han^a ; ^{than927@163.com" class="auth_mail} ; Lu-Ping Qin^a ; ^{qinsmmu@126.com" class="auth_mail}
• 关键词：Xanthium strumarium L. ; Metabonomics ; 1H NMR ; Hepatotoxicity
• 刊名：Journal of Ethnopharmacology
• 出版年：14 March, 2014
• 年：2014
• 卷：152
• 期：2
• 页码：272-282
• 全文大小：2081 K

文摘

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.

Materials and methods

XSF extract was prepared and seven characteristic components were isolated and identi铿乪d 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 ¹H nuclear magnetic resonance (¹H 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.

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.

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 ¹H 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.