title: 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.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences , Beijing 100700, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Wei
authors.forename: Fangbo
authors.initials: F
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chunyu
authors.initials: C
authors.lastname: Cao
authors.forename: Xianyu
authors.initials: X
authors.lastname: Li
authors.forename: Defeng
authors.initials: D
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yang
authors.forename: Luqi
authors.initials: L
authors.lastname: Huang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D050938:Glycine N-Methyltransferase / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D039823:Iridoids; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D039823:Iridoids; D020543:Proteome; C007835:geniposide; D050938:Glycine N-Methyltransferase; D024981:Glycogen Phosphorylase
keywords: biomarker; geniposide; hepatotoxicity; proteome