Proteomic Investigation of Signatures for Geniposide-Induced Hepatotoxicity
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- 作者：Junying Wei ; Fangbo Zhang ; Yi Zhang ; Chunyu Cao ; Xianyu Li ; Defeng Li ; Xin Liu ; Hongjun Yang ; Luqi Huang
- 刊名：Journal of Proteome Research
- 出版年：2014
- 出版时间：December 5, 2014
- 年：2014
- 卷：13
- 期：12
- 页码：5724-5733
- 全文大小：506K
- ISSN：1535-3907
文摘
Evaluating the safety of traditional medicinal herbs and their major active constituents is critical for their widespread usage. Geniposide, a major active constituent with a defined structure from the traditional medicinal herb Gardenia jasminoides ELLIS fruit, exhibits remarkable anti-inflammatory, antiapoptotic, and antifibrotic properties and has been used in a variety of medical fields, mainly for the treatment of liver diseases. However, geniposide-induced hepatotoxicity and methods for the early detection of hepatotoxicity have yet to be reported. In this study, geniposide-induced hepatotoxicity was investigated. In addition, candidate biomarkers for the earlier detection of geniposide-induced hepatotoxicity were identified using a label-free quantitative proteomics approach on a geniposide overdose-induced liver injury in a rat model. Using an accurate intensity-based, absolute quantification (iBAQ)-based, one-step discovery and verification approach, a candidate biomarker panel was easily obtained from individual samples in response to different conditions. To determine the biomarkers鈥?early detection abilities, five candidate biomarkers were selected and tested using enzyme-linked immunosorbent assays (ELISAs). Two biomarkers, glycine N-methyltransferase (GNMT) and glycogen phosphorylase (PYGL), were found to indicate hepatic injuries significantly earlier than the current gold standard liver biomarker. This study provides a first insight into geniposide-induced hepatotoxicity in a rat model and describes a method for the earlier detection of this hepatotoxicity, facilitating the efficient monitoring of drug-induced hepatotoxicity.