Proteomic investigation of signatures for geniposide-induced hepatotoxicity.

Abstract

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' 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.

• Authors: Junying Wei, Fangbo Zhang, Yi Zhang, Chunyu Cao, Xianyu Li, Defeng Li, Xin Liu, Hongjun Yang, Luqi Huang
• Journal: Journal of proteome research (J Proteome Res) Vol. 13 Issue 12 Pg. 5724-33 (Dec 05 2014) ISSN: 1535-3907 [Electronic] United States
• PMID: 25336395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Iridoids
• Proteome
• geniposide
• Glycine N-Methyltransferase
• Glycogen Phosphorylase

Topics

• Animals
• Biomarkers (blood, metabolism)
• Chemical and Drug Induced Liver Injury (blood, diagnosis, metabolism)
• Early Diagnosis
• Enzyme-Linked Immunosorbent Assay
• Glycine N-Methyltransferase (metabolism)
• Glycogen Phosphorylase (metabolism)
• Iridoids
• Liver (metabolism, pathology)
• Male
• Proteome (metabolism)
• Proteomics (methods)
• Rats, Sprague-Dawley
• Reproducibility of Results
• Sensitivity and Specificity