Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.
Investigation of Dioscorea bulbifera Rhizome-Induced Hepatotoxicity in Rats by a Multisample Integrated Metabolomics Approach.
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DOI：
10.1021/acs.chemrestox.7b00176
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发表时间：
2017-09
影响因子：
4.1
通讯作者：
Dong-Sheng Zhao;Li-Long Jiang;Ya-Xi Fan;Lingli Wang;Zhuo-Qing Li;W. Shi;Ping Li;Hui-Jun Li
中科院分区：
文献类型：
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作者：
Dong-Sheng Zhao;Li-Long Jiang;Ya-Xi Fan;Lingli Wang;Zhuo-Qing Li;W. Shi;Ping Li;Hui-Jun Li
草药的使用在全球范围内不断扩大，与此同时，草药相关的肝毒性正在成为一个安全问题。黄薯蓣根茎（Dioscorea bulbifera rhizome， DBR）是一种传统的中草药，具有肝毒性。然而，确切的潜在机制在很大程度上仍未被探索。在本研究中，我们旨在利用多样本综合代谢组学策略来分析生物系统中的整个内源性代谢物。我们的发现为dbr诱导的肝毒性的分子机制提供了额外的见解。采用气相色谱-质谱联用多变量分析方法，从大鼠血浆、尿液和粪便中鉴定出不同的代谢物。共鉴定出分布在33种代谢途径中的55种代谢物在dbr处理大鼠中发生了显著改变。相关网络分析显示，肝毒性中枢代谢物主要与氨基酸、胆汁酸、嘌呤、嘧啶、脂质和能量代谢相关。因此，DBR通过调节多种代谢途径使肝脏处于异常状态，从而影响肝脏的生理生物学功能。值得注意的是，我们的研究结果还表明，多样本综合代谢组学策略具有很大的潜力，可以识别更多的生物标志物和途径，以阐明中药毒性的机制复杂性。
The use of herbal medicines continues to expand globally, meanwhile, herb-associated hepatotoxicity is becoming a safety issue. As a conventional Chinese medicinal herb, Dioscorea bulbifera rhizome (DBR) has been documented to cause hepatic toxicity. However, the exact underlying mechanism remains largely unexplored. In the present study, we aimed to profile entire endogenous metabolites in a biological system using a multisample integrated metabolomics strategy. Our findings offered additional insights into the molecular mechanism of the DBR-induced hepatotoxicity. We identified different metabolites from rat plasma, urine, and feces by employing gas chromatography-mass spectrometry in combination with multivariate analysis. In total, 55 metabolites distributed in 33 metabolic pathways were identified as being significantly altered in DBR-treated rats. Correlation network analysis revealed that the hub metabolites of hepatotoxicity were mainly associated with amino acid, bile acid, purine, pyrimidine, lipid, and energy metabolism. As such, DBR affected the physiological and biological functions of liver via the regulation of multiple metabolic pathways to an abnormal state. Notably, our findings also demonstrated that the multisample integrated metabolomics strategy has a great potential to identify more biomarkers and pathways in order to elucidate the mechanistic complexity of toxicity of traditional Chinese medicine.