Zhao Dong-Sheng, Jiang Li-Long, Fan Ya-Xi, Wang Ling-Li, Li Zhuo-Qing, Shi Wei, Li Ping, Li Hui-Jun
State Key Laboratory of Natural Medicines, China Pharmaceutical University , No. 24 Tongjia Lane, Nanjing 210009, China.
Chem Res Toxicol. 2017 Oct 16;30(10):1865-1873. doi: 10.1021/acs.chemrestox.7b00176. Epub 2017 Sep 22.
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.
草药的使用在全球范围内持续增加，与此同时，草药相关的肝毒性正成为一个安全问题。作为一种传统的中药材，黄药子已被证明会导致肝毒性。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，我们旨在使用多样本综合代谢组学策略描绘生物系统中的全部内源性代谢物。我们的研究结果为黄药子诱导肝毒性的分子机制提供了更多见解。我们通过气相色谱 - 质谱联用结合多变量分析从大鼠血浆、尿液和粪便中鉴定出不同的代谢物。总共，在33条代谢途径中分布的55种代谢物被鉴定为在黄药子处理的大鼠中发生了显著变化。相关网络分析表明，肝毒性的枢纽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，黄药子通过将多种代谢途径调节至异常状态来影响肝脏的生理和生物学功能。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在识别更多生物标志物和途径以阐明中药毒性机制复杂性方面具有巨大潜力。
