Proteomic Investigation of Signatures for Geniposide-Induced Hepatotoxicity

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.