Metabolomics and proteomics annotate therapeutic properties of geniposide: targeting and regulating multiple perturbed pathways

• Published in: PloS one 2013-08, Vol.8 (8), p.e71403-e71403
• Main Authors: Wang, Xijun, Zhang, Aihua, Yan, Guangli, Sun, Wenjun, Han, Ying, Sun, Hui
• Format: Article
• Language: English
• Subjects: Alanine; Animals; Bile acids; Biochemical analysis; Biochemistry; Bioindicators; Bioinformatics; Biology; Biomarkers; Biosynthesis; Breast cancer; Chemistry; Chinese medicine; Chromatography; Citric acid; Cluster Analysis; Disease; Drug discovery; Energy metabolism; Gangrene; Gardenia Jasminoides Ellis; Health aspects; Herbal medicine; Identification; Immunity; Injury prevention; Ions; Iridoids - pharmacology; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mass spectrometry; Medicinal plants; Medicine; Metabolic Networks and Pathways - drug effects; Metabolism; Metabolites; Metabolomics; Natural products; Pattern recognition; Pharmacology; Plants, Medicinal - metabolism; Protein interaction; Protein Interaction Mapping; Protein Interaction Maps; Protein-protein interactions; Proteins; Proteomics; Rats; Rodents; Scientific imaging; Signal Transduction - drug effects; Studies; Target recognition; Tricarboxylic acid cycle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071403

Geniposide is an important constituent of Gardenia jasminoides Ellis, a famous Chinese medicinal plant, and has displayed bright prospects in prevention and therapy of hepatic injury (HI). Unfortunately, the working mechanisms of this compound are difficult to determine and thus remain unknown. To determine the mechanisms that underlie this compound, we conducted a systematic analysis of the therapeutic effects of geniposide using biochemistry, metabolomics and proteomics. Geniposide significantly intensified the therapeutic efficacy as indicated by our modern biochemical analysis. Metabolomics results indicate 9 ions in the positive mode as differentiating metabolites which were associated with perturbations in primary bile acid biosynthesis, butanoate metabolism, citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism. Of note, geniposide has potential pharmacological effect through regulating multiple perturbed pathways to normal state. In an attempt to address the benefits of geniposide based on the proteomics approaches, the protein-interacting networks were constructed to aid identifying the drug targets of geniposide. Six identified differential proteins appear to be involved in antioxidation and signal transduction, energy production, immunity, metabolism, chaperoning. These proteins were closely related in the protein-protein interaction network and the modulation of multiple vital physiological pathways. These data will help to understand the molecular therapeutic mechanisms of geniposide on hepatic damage rats. We also conclude that metabolomics and proteomics are powerful and versatile tools for both biomarker discovery and exploring the complex relationships between biological pathways and drug response, highlighting insights into drug discovery.