State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.
J Ethnopharmacol. 2018 Nov 15;226:111-119. doi: 10.1016/j.jep.2018.08.014. Epub 2018 Aug 13.
Dioscorea bulbifera rhizome (DBR), one type of herbal medicine, is extensively used in both Indian and Chinese system of traditional medicine. It has been effective in treating various diseases, such as sore throat, struma, and tumors. However, more and more clinical investigations have suggested that DBR can cause liver injury.
In the present study, we aimed to characterize the corresponding molecular changes of liver dysfunction and reveal overall metabolic and physiological mechanisms of the subchronic toxic effect of DBR.
A liver-specific metabolomics approach integrating GC-MS and H-NMR was developed to assess the hepatotoxicity in rats after DBR exposure for 12 weeks. Multivariate statistical analysis and pattern recognition were employed to examine different metabolic profiles of liver in DBR-challenged rats.
A total of 61 metabolites were screened as significantly altered metabolites, which were distributed in 43 metabolic pathways. The correlation network analysis indicated that the hub metabolites of hepatotoxicity could be mainly linked to amino acid, lipid, purine, pyrimidine, bile acid, gut microflora, and energy metabolisms. Notably, purine, pyrimidine, and gut microflora metabolisms might be novel pathways participating in metabolic abnormalities in rats with DBR-triggered hepatic damage.
Our results primarily showed that the liver-specific metabolic information provided by the different analytical platforms was essential for identifying more biomarkers and metabolic pathways, and our findings provided novel insights into understand the mechanistic complexity of herb-induced liver injury.
薯蓣属植物的根茎（DBR）是一种草药，在印度和中国传统医学中被广泛使用。它已被证明对治疗各种疾病有效，如喉咙痛、甲状腺肿和肿瘤。然而，越来越多的临床研究表明 DBR 可能会导致肝损伤。
在本研究中，我们旨在描述肝功能障碍的相应分子变化，并揭示 DBR 亚慢性毒性作用的整体代谢和生理机制。
采用 GC-MS 和 H-NMR 相结合的肝脏特异性代谢组学方法，评估 DBR 暴露 12 周后大鼠的肝毒性。采用多变量统计分析和模式识别方法来检查 DBR 挑战大鼠肝脏的不同代谢谱。
共筛选出 61 种代谢物作为显著改变的代谢物，分布在 43 条代谢途径中。相关网络分析表明，肝毒性的关键代谢物主要与氨基酸、脂质、嘌呤、嘧啶、胆汁酸、肠道微生物群和能量代谢有关。值得注意的是，嘌呤、嘧啶和肠道微生物群代谢可能是参与 DBR 引起的肝损伤大鼠代谢异常的新途径。
我们的研究结果主要表明，不同分析平台提供的肝脏特异性代谢信息对于鉴定更多的生物标志物和代谢途径至关重要，并且我们的研究结果为理解草药引起的肝损伤的机制复杂性提供了新的见解。
