RGD Reference Report - Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression. - Rat Genome Database

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Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression.

Authors: Peng, Jing-Hua  Cui, Tuan  Huang, Fu  Chen, Liang  Zhao, Yu  Xu, Lin  Xu, Li-Li  Feng, Qin  Hu, Yi-Yang 
Citation: Peng JH, etal., J Pharmacol Exp Ther. 2013 Mar;344(3):646-54. doi: 10.1124/jpet.112.201137. Epub 2012 Dec 31.
RGD ID: 407424596
Pubmed: PMID:23277536   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.112.201137   (Journal Full-text)

Puerarin, an isoflavone component extracted from Kudzu (Pueraria lobata), has been demonstrated to alleviate alcohol-related disorders. Our study examined whether puerarin ameliorates chronic alcoholic liver injury through inhibition of endotoxin gut leakage, the subsequent Kupffer cell activation, and endotoxin receptors expression. Rats were provided with the Liber-DeCarli liquid diet for 8 weeks. Puerarin (90 mg/kg or 180 mg/kg daily) was orally administered from the beginning of the third week until the end of the experiment. Chronic alcohol intake caused increased serum alanine aminotransferase, aspartate aminotransferase, hepatic gamma-glutamyl transpeptidase, and triglyceride levels as well as fatty liver and neutrophil infiltration in hepatic lobules as determined by biochemical and histologic assays. A significant increase of liver tumor necrosis factor α was detected by enzyme-linked immunosorbent assay. These pathologic effects correlated with increased endotoxin level in portal vein and upregulated protein expression of hepatic CD68, lipopolysaccharide-binding protein, CD14, Toll-like receptor 2, and Toll-like receptor 4. Meanwhile, the intestinal microvilli were observed to be sparse, shortened, and irregularity in distribution under the transmission electron microscope in conjunction with the downregulated intestinal zonula occludens-1 protein expression. These hepatic pathologic changes were significantly inhibited in puerarin-treated animals as were the endotoxin levels and hepatic CD68 and endotoxin receptors. Moreover, the pathologic changes in intestinal microvillus and the decreased intestinal zonula occludens-1 were also ameliorated with puerarin treatment. These results thus demonstrate that puerarin inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression is involved in the alleviation of chronic alcoholic liver injury in rats.



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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
CD14Humanmetabolic dysfunction and alcohol associated liver disease treatmentISOCd14 (Rattus norvegicus) RGD 
CD68Humanmetabolic dysfunction and alcohol associated liver disease treatmentISOCd68 (Rattus norvegicus) RGD 
Cd14Mousemetabolic dysfunction and alcohol associated liver disease treatmentISOCd14 (Rattus norvegicus) RGD 
Cd14Ratmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
Cd68Mousemetabolic dysfunction and alcohol associated liver disease treatmentISOCd68 (Rattus norvegicus) RGD 
Cd68Ratmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
LBPHumanmetabolic dysfunction and alcohol associated liver disease treatmentISOLbp (Rattus norvegicus) RGD 
LbpMousemetabolic dysfunction and alcohol associated liver disease treatmentISOLbp (Rattus norvegicus) RGD 
LbpRatmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
TJP1Humanmetabolic dysfunction and alcohol associated liver disease treatmentISOTjp1 (Rattus norvegicus) RGD 
TLR2Humanmetabolic dysfunction and alcohol associated liver disease treatmentISOTlr2 (Rattus norvegicus) RGD 
TLR4Humanmetabolic dysfunction and alcohol associated liver disease treatmentISOTlr4 (Rattus norvegicus) RGD 
Tjp1Mousemetabolic dysfunction and alcohol associated liver disease treatmentISOTjp1 (Rattus norvegicus) RGD 
Tjp1Ratmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
Tlr2Mousemetabolic dysfunction and alcohol associated liver disease treatmentISOTlr2 (Rattus norvegicus) RGD 
Tlr2Ratmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
Tlr4Mousemetabolic dysfunction and alcohol associated liver disease treatmentISOTlr4 (Rattus norvegicus) RGD 
Tlr4Ratmetabolic dysfunction and alcohol associated liver disease treatmentIEP  RGD 
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Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
CD14Humanethanol increases expression ISOCd14 (Rattus norvegicus)ethanol increases expression of cd14 protein in liverRGD 
CD14Humanethanol multiple interactionsISOCd14 (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of cd14 protein in liver]RGD 
CD68Humanethanol increases expression ISOCd68 (Rattus norvegicus)ethanol increases expression of CD68 protein in liverRGD 
CD68Humanethanol multiple interactionsISOCd68 (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of CD68 protein in liver]RGD 
Cd14Ratethanol increases expression EXP ethanol increases expression of cd14 protein in liverRGD 
Cd14Mouseethanol multiple interactionsISOCd14 (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of cd14 protein in liver]RGD 
Cd14Mouseethanol increases expression ISOCd14 (Rattus norvegicus)ethanol increases expression of cd14 protein in liverRGD 
Cd14Ratethanol multiple interactionsEXP puerarin inhibits the reaction [ethanol increases expression of cd14 protein in liver]RGD 
Cd68Ratethanol increases expression EXP ethanol increases expression of CD68 protein in liverRGD 
Cd68Mouseethanol multiple interactionsISOCd68 (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of CD68 protein in liver]RGD 
Cd68Mouseethanol increases expression ISOCd68 (Rattus norvegicus)ethanol increases expression of CD68 protein in liverRGD 
Cd68Ratethanol multiple interactionsEXP puerarin inhibits the reaction [ethanol increases expression of CD68 protein in liver]RGD 
LBPHumanethanol increases expression ISOLbp (Rattus norvegicus)ethanol increases expression of Lbp protein in liverRGD 
LBPHumanethanol multiple interactionsISOLbp (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of Lbp protein in liver]RGD 
LbpRatethanol increases expression EXP ethanol increases expression of Lbp protein in liverRGD 
LbpMouseethanol multiple interactionsISOLbp (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of Lbp protein in liver]RGD 
LbpMouseethanol increases expression ISOLbp (Rattus norvegicus)ethanol increases expression of Lbp protein in liverRGD 
LbpRatethanol multiple interactionsEXP puerarin inhibits the reaction [ethanol increases expression of Lbp protein in liver]RGD 
TJP1Humanethanol increases expression ISOTjp1 (Rattus norvegicus)ethanol increases expression of Tjp1 protein in intestineRGD 
TJP1Humanethanol multiple interactionsISOTjp1 (Rattus norvegicus)puerarin inhibits the reaction [ethanol increases expression of Tjp1 protein in intestine]RGD 

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Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cd14Ratresponse to ethanol  IEP  RGD 
Cd68Ratresponse to ethanol  IEP  RGD 
LbpRatresponse to ethanol  IEP  RGD 
Tjp1Ratresponse to ethanol  IEP  RGD 
Tlr2Ratresponse to ethanol  IEP  RGD 
Tlr4Ratresponse to ethanol  IEP  RGD 
TnfRatresponse to ethanol  IEP  RGD 


Genes (Rattus norvegicus)
Cd14  (CD14 molecule) Cd68  (Cd68 molecule) Lbp  (lipopolysaccharide binding protein)
Tjp1  (tight junction protein 1) Tlr2  (toll-like receptor 2) Tlr4  (toll-like receptor 4)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Cd14  (CD14 antigen) Cd68  (CD68 antigen) Lbp  (lipopolysaccharide binding protein)
Tjp1  (tight junction protein 1) Tlr2  (toll-like receptor 2) Tlr4  (toll-like receptor 4)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
CD14  (CD14 molecule) CD68  (CD68 molecule) LBP  (lipopolysaccharide binding protein)
TJP1  (tight junction protein 1) TLR2  (toll like receptor 2) TLR4  (toll like receptor 4)
TNF  (tumor necrosis factor)