RGD Reference Report - Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures. - Rat Genome Database

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Exploration of Hepatoprotective Effect of Gentiopicroside on Alpha-Naphthylisothiocyanate-Induced Cholestatic Liver Injury in Rats by Comprehensive Proteomic and Metabolomic Signatures.

Authors: Han, Han  Xu, Lili  Xiong, Kai  Zhang, Tong  Wang, Zhengtao 
Citation: Han H, etal., Cell Physiol Biochem. 2018;49(4):1304-1319. doi: 10.1159/000493409. Epub 2018 Sep 17.
RGD ID: 15045612
Pubmed: PMID:30223280   (View Abstract at PubMed)
DOI: DOI:10.1159/000493409   (Journal Full-text)


BACKGROUND/AIMS: Cholestasis is the major cause of the accumulation of bile acids and results in liver damage, fibrosis, and failure. A growing number of studies have shown that gentiopicroside is a promising prospect that may protect the liver. However, its therapeutic mechanism has not yet been clarified. This study aimed to explore the effect and mechanism of gentiopicroside in cholestasis induced by alpha-naphthylisothiocyanate.
METHODS: We performed isobaric tags for relative and absolute quantification-based quantitative proteomics and metabolomics using liquid chromatography quadruple time-of-fight mass spectrometry and identified the expression of 73 metabolites and 84 proteins associated with cholestasis-related dysfunctions in the metabolism of bile acids, fatty acids, and glycerophospholipids.
RESULTS: Integrated analyses of proteomic and metabonomic studies showed altered pathways in cholestasis-induced liver injury involving increased activity of farnesoid X receptor/retinoid X receptor, bile acid biosynthesis, and peroxisome proliferator-activated receptor-α/retinoid X receptor-α. Gentiopicroside could reverse these metabolite, protein, and blood biochemical indices, as well as alleviate liver damage. The progressive changes in the proteins and genes may be correlated with cholestasis and were confirmed by western blot and quantitative realtime polymerase chain reaction.
CONCLUSION: Gentiopicroside could be used to protect the liver in the presence of cholestasis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholestasis treatmentISOAbcc4 (Rattus norvegicus)15045612; 15045612 RGD 
cholestasis treatmentISOAldh1l1 (Rattus norvegicus)15045612; 15045612 RGD 
cholestasis treatmentIEP 15045612; 15045612; 15045612 RGD 
cholestasis treatmentISONr1h4 (Rattus norvegicus)15045612; 15045612 RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
1-naphthyl isothiocyanate decreases expressionISOAldh1l1 (Rattus norvegicus)15045612; 150456121-naphthyl isothiocyanate decreases expression of ALDH1L1 mRNA in rat liverRGD 
1-naphthyl isothiocyanate decreases expressionEXP 150456121-naphthyl isothiocyanate decreases expression of ALDH1L1 mRNA in rat liverRGD 
1-naphthyl isothiocyanate decreases expressionISONr1h4 (Rattus norvegicus)15045612; 150456121-naphthyl isothiocyanate decreases expression of Nr1h4 mRNA in rat liverRGD 
1-naphthyl isothiocyanate decreases expressionEXP 150456121-naphthyl isothiocyanate decreases expression of Nr1h4 mRNA in rat liverRGD 
Gentiopicrin multiple interactionsISOAbcc4 (Rattus norvegicus)15045612; 15045612Gentiopicrin reverses the interaction [1-naphthyl isothiocyanate decreases expression of MRP4 mRNA in rat liver]RGD 
Gentiopicrin multiple interactionsEXP 15045612Gentiopicrin reverses the interaction [1-naphthyl isothiocyanate decreases expression of MRP4 mRNA in rat liver]RGD 
Gentiopicrin decreases expressionISOCyp7a1 (Rattus norvegicus)15045612; 15045612Gentiopicrin decreases expression of Cyp7a1 mRNA in rat ANIT induced cholestatic liverRGD 
Gentiopicrin decreases expressionEXP 15045612Gentiopicrin decreases expression of Cyp7a1 mRNA in rat ANIT induced cholestatic liverRGD 
Gentiopicrin multiple interactionsISONr1h4 (Rattus norvegicus)15045612; 15045612Gentiopicrin reverses the reaction [1-naphthyl isothiocyanate decreases expression of Nr1h4 mRNA in rat liver]RGD 
Gentiopicrin multiple interactionsEXP 15045612Gentiopicrin reverses the reaction [1-naphthyl isothiocyanate decreases expression of Nr1h4 mRNA in rat liver]RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bile acid signaling pathway  IEP 15045612; 15045612; 15045612; 15045612 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Abcc4  (ATP binding cassette subfamily C member 4)
Aldh1l1  (aldehyde dehydrogenase 1 family, member L1)
Cyp7a1  (cytochrome P450 family 7 subfamily A member 1)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)
Abcc4  (ATP-binding cassette, sub-family C member 4)
Aldh1l1  (aldehyde dehydrogenase 1 family, member L1)
Cyp7a1  (cytochrome P450, family 7, subfamily a, polypeptide 1)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)

Genes (Homo sapiens)
ABCC4  (ATP binding cassette subfamily C member 4 (PEL blood group))
ALDH1L1  (aldehyde dehydrogenase 1 family member L1)
CYP7A1  (cytochrome P450 family 7 subfamily A member 1)
NR1H4  (nuclear receptor subfamily 1 group H member 4)


Additional Information