基于超高效液相色谱-四极杆飞行时间质谱代谢组学的制何首乌致肝损伤生物标志物及机制分析
Biomarkers and Mechanism Analysis for Polygoni Multiflori Radix Preparata-Induced Liver Injury by UHPLC-Q-TOF-MS-Based Metabolomics.
作者信息
Wang Liming, Wang Zhida, Xing Yanchao, Liu Erwei, Gao Xiumei, Wang Linlin, Fu Zhifei
机构信息
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, China.
NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
出版信息
Evid Based Complement Alternat Med. 2021 Nov 23;2021:7677392. doi: 10.1155/2021/7677392. eCollection 2021.
BACKGROUND
Polygonum Multiflorum Radix Preparata (PMP), prepared from Thunb. (PM), is traditionally valued for its liver and kidney-tonifying effects. However, the previous studies showed that PMP was hepatotoxic, which limited its clinical use. Unfortunately, the potential hepatotoxic ingredients and the molecular mechanism are still uncertain.
OBJECTIVE
The aim of this study was to find out potential biomarkers of hepatotoxicity using metabolomics profile.
MATERIALS AND METHODS
60% ethanol extract of PMP (PMPE) was prepared. Subsequently, an untargeted metabolomics technology in combination with ROC curve analysis method was applied to investigate the alteration of plasma metabolites in rats after oral administration of PMPE (40 g/kg/d) for 28 days.
RESULTS
Compared to the control group, the significant difference in metabolic profiling was observed in the PMPE-induced liver injury group, and sixteen highly specific biomarkers were identified. These metabolites were mainly enriched into bile acids, lipids, and energy metabolisms, indicating that PMPE-induced liver injury could be related to cholestasis and dysregulated lipid metabolism.
CONCLUSIONS
This study is contributed to understand the potential pathogenesis of PMP-induced liver injury. The metabonomic method may be a valuable tool for the clinical diagnosis of PMP-induced liver injury.
背景
制何首乌（PMP）由何首乌（PM）炮制而成，传统上因其具有补肝肾作用而受到重视。然而，先前的研究表明PMP具有肝毒性，这限制了其临床应用。遗憾的是，潜在的肝毒性成分及其分子机制仍不明确。
目的
本研究旨在利用代谢组学图谱找出肝毒性的潜在生物标志物。
材料与方法
制备PMP的60%乙醇提取物（PMPE）。随后，采用非靶向代谢组学技术结合ROC曲线分析方法，研究大鼠口服PMPE（40 g/kg/d）28天后血浆代谢物的变化。
结果
与对照组相比，PMPE诱导的肝损伤组代谢谱存在显著差异，鉴定出16种高度特异性的生物标志物。这些代谢物主要富集在胆汁酸、脂质和能量代谢中，表明PMPE诱导的肝损伤可能与胆汁淤积和脂质代谢失调有关。
结论
本研究有助于了解PMP诱导肝损伤的潜在发病机制。代谢组学方法可能是临床诊断PMP诱导肝损伤的有价值工具。
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