title: Metabolomics and proteomics annotate therapeutic properties of geniposide: targeting and regulating multiple perturbed pathways.
abstract: 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.
authors: National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics and Key Pharmacometabolomics Platform of Chinese Medicines, Heilongjiang University of Chinese Medicine, Harbin, China. metabolomics@126.com
authors: Xijun
authors: X
authors: Wang
authors: Aihua
authors: A
authors: Zhang
authors: Guangli
authors: G
authors: Yan
authors: Wenjun
authors: W
authors: Sun
authors: Ying
authors: Y
authors: Han
authors: Hui
authors: H
authors: Sun
mesh_terms: D000818:Animals; D015415:Biomarkers; D016000:Cluster Analysis; D039823:Iridoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics; D010946:Plants, Medicinal / Q000378:metabolism; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D040901:Proteomics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D039823:Iridoids; C007835:geniposide
references: Mol Biosyst. 2013 Sep;9(9):2259-65
references: 23821129
references: Mol Cell Proteomics. 2013 Mar;12(3):710-9
references: 23264353
references: Obes Rev. 2013 Apr;14(4):344-9
references: 23279162
references: Clin Chim Acta. 2013 Sep 23;424:3-7
references: 23669185
references: PLoS One. 2013 May 16;8(5):e64381
references: 23696887
references: J Pharm Biomed Anal. 2013 Feb 23;74:22-30
references: 23245229
references: Science. 2008 Oct 17;322(5900):453-6
references: 18927396
references: Rapid Commun Mass Spectrom. 2003;17(24):2732-40
references: 14673820
references: Nature. 2011 Oct 30;480(7376):254-8
references: 22037311
references: Science. 2011 Dec 2;334(6060):1230-2
references: 22144616
references: Nat Prod Rep. 2012 Jun;29(6):659-82
references: 22504336
references: Appl Biochem Biotechnol. 2013 Jun;170(4):774-86
references: 23609910
references: Analyst. 2013 Jan 7;138(1):353-61
references: 23152956
references: Nat Chem Biol. 2009 Sep;5(9):616-24
references: 19690537
references: Eur J Med Chem. 2013 May;63:570-7
references: 23567947
references: Mol Cell Proteomics. 2013 May;12(5):1226-38
references: 23362329
references: Br J Pharmacol. 2011 Nov;164(5):1547-57
references: 21649640
references: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31
references: 18344322
references: Analyst. 2012 Oct 21;137(20):4703-11
references: 22950079
references: Nat Med. 2011 Jun;17(6):708-14
references: 21572428
references: OMICS. 2013 Apr;17(4):224-9
references: 23514563
references: PLoS One. 2013;8(2):e56111
references: 23405259
references: Fitoterapia. 2011 Dec;82(8):1160-8
references: 21835230
references: Analyst. 2011 Dec 7;136(23):5068-76
references: 21991580
references: OMICS. 2012 Jul-Aug;16(7-8):414-21
references: 22734809
references: Magn Reson Chem. 2013 Sep;51(9):549-56
references: 23828598
references: Nat Med. 2012 Sep;18(9):1434-40
references: 22902875