RGD Reference Report - Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner. - Rat Genome Database
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Dihydroartemisinin protects against alcoholic liver injury through alleviating hepatocyte steatosis in a farnesoid X receptor-dependent manner.

Authors: Xu, Wenxuan  Lu, Chunfeng  Yao, Lu  Zhang, Feng  Shao, Jiangjuan  Zheng, Shizhong 
Citation: Xu W, etal., Toxicol Appl Pharmacol. 2017 Jan 15;315:23-34. doi: 10.1016/j.taap.2016.12.001. Epub 2016 Dec 6.
RGD ID: 15036816
Pubmed: (View Article at PubMed) PMID:27939985
DOI: Full-text: DOI:10.1016/j.taap.2016.12.001

Alcoholic liver disease (ALD) is a common etiology of liver diseases, characterized by hepatic steatosis. We previously identified farnesoid X receptor (FXR) as a potential therapeutic target for ALD. Dihydroartemisinin (DHA) has been recently identified to possess potent pharmacological activities on liver diseases. This study was aimed to explore the impact of DHA on ALD and further elaborate the underlying mechanisms. Gain- or loss-of-function analyses of FXR were applied in both in vivo and in vitro studies. Results demonstrated that DHA rescued FXR expression and activity in alcoholic rat livers. DHA also reduced serodiagnostic markers of liver injury, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase. DHA improved alcohol-induced liver histological lesions, expression of inflammation genes, and inflammatory cell infiltration. In addition, DHA not only attenuated hyperlipidemia but also reduced hepatic steatosis through regulating lipogenesis and lipolysis genes. In vitro experiments further consolidated the concept that DHA ameliorated ethanol-caused hepatocyte injury and steatosis. Noteworthily, DHA effects were reinforced by FXR agonist obeticholic acid or FXR expression plasmids but abrogated by FXR antagonist Z-guggulsterone or FXR siRNA. In summary, DHA significantly improved alcoholic liver injury by inhibiting hepatic steatosis, which was dependent on its activation of FXR in hepatocytes.

Annotation

Disease Annotations    

Gene-Chemical Interaction Annotations    
dihydroartemisinin  (EXP,ISO)
ethanol  (EXP,ISO)
guggulsterone  (EXP,ISO)
obeticholic acid  (EXP,ISO)

Gene Ontology Annotations    

Cellular Component
nucleus  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Abcb11  (ATP binding cassette subfamily B member 11)
Cpt1a  (carnitine palmitoyltransferase 1A)
Cyp7a1  (cytochrome P450 family 7 subfamily A member 1)
Fas  (Fas cell surface death receptor)
Fgf19  (fibroblast growth factor 19)
Nfkb1  (nuclear factor kappa B subunit 1)
Nfkbia  (NFKB inhibitor alpha)
Nlrp3  (NLR family, pyrin domain containing 3)
Nr0b2  (nuclear receptor subfamily 0, group B, member 2)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)
Ppara  (peroxisome proliferator activated receptor alpha)
Slc10a1  (solute carrier family 10 member 1)
Srebf1  (sterol regulatory element binding transcription factor 1)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Abcb11  (ATP-binding cassette, sub-family B (MDR/TAP), member 11)
Cpt1a  (carnitine palmitoyltransferase 1a, liver)
Cyp7a1  (cytochrome P450, family 7, subfamily a, polypeptide 1)
Fas  (Fas (TNF receptor superfamily member 6))
Fgf15  (fibroblast growth factor 15)
Nfkb1  (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105)
Nfkbia  (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha)
Nlrp3  (NLR family, pyrin domain containing 3)
Nr0b2  (nuclear receptor subfamily 0, group B, member 2)
Nr1h4  (nuclear receptor subfamily 1, group H, member 4)
Ppara  (peroxisome proliferator activated receptor alpha)
Slc10a1  (solute carrier family 10 (sodium/bile acid cotransporter family), member 1)
Srebf1  (sterol regulatory element binding transcription factor 1)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
ABCB11  (ATP binding cassette subfamily B member 11)
CPT1A  (carnitine palmitoyltransferase 1A)
CYP7A1  (cytochrome P450 family 7 subfamily A member 1)
FAS  (Fas cell surface death receptor)
FGF19  (fibroblast growth factor 19)
NFKB1  (nuclear factor kappa B subunit 1)
NFKBIA  (NFKB inhibitor alpha)
NLRP3  (NLR family pyrin domain containing 3)
NR0B2  (nuclear receptor subfamily 0 group B member 2)
NR1H4  (nuclear receptor subfamily 1 group H member 4)
PPARA  (peroxisome proliferator activated receptor alpha)
SLC10A1  (solute carrier family 10 member 1)
SREBF1  (sterol regulatory element binding transcription factor 1)
TNF  (tumor necrosis factor)


Additional Information