RGD Reference Report - Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.

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Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.
Authors:	Zhu, Lili Wang, Lei Cao, Fei Liu, Peng Bao, Haidong Yan, Yumei Dong, Xin Wang, Dong Wang, Zhongyu Gong, Peng
Citation:	Zhu L, etal., J Hepatobiliary Pancreat Sci. 2018 Mar;25(3):195-205. doi: 10.1002/jhbp.537.
RGD ID:	14995480
Pubmed:	PMID:29360226 (View Abstract at PubMed)
DOI:	DOI:10.1002/jhbp.537 (Journal Full-text)
BACKGROUND: The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. CONCLUSIONS: Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
ABCC4	Human	extrahepatic cholestasis	treatment	ISO	Abcc4 (Rattus norvegicus)	mRNA:increased expression:liver (rat)	RGD
Abcc4	Rat	extrahepatic cholestasis	treatment	IEP		mRNA:increased expression:liver (rat)	RGD
Abcc4	Mouse	extrahepatic cholestasis	treatment	ISO	Abcc4 (Rattus norvegicus)	mRNA:increased expression:liver (rat)	RGD
CYP27A1	Human	extrahepatic cholestasis	treatment	ISO	Cyp27a1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
CYP7A1	Human	extrahepatic cholestasis	treatment	ISO	Cyp7a1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
CYP8B1	Human	extrahepatic cholestasis	treatment	ISO	Cyp8b1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
Cyp27a1	Rat	extrahepatic cholestasis	treatment	IEP		mRNA:decreased expression:liver (rat)	RGD
Cyp27a1	Mouse	extrahepatic cholestasis	treatment	ISO	Cyp27a1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
Cyp7a1	Rat	extrahepatic cholestasis	treatment	IEP		mRNA:decreased expression:liver (rat)	RGD
Cyp7a1	Mouse	extrahepatic cholestasis	treatment	ISO	Cyp7a1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
Cyp8b1	Rat	extrahepatic cholestasis	treatment	IEP		mRNA:decreased expression:liver (rat)	RGD
Cyp8b1	Mouse	extrahepatic cholestasis	treatment	ISO	Cyp8b1 (Rattus norvegicus)	mRNA:decreased expression:liver (rat)	RGD
NR1H4	Human	extrahepatic cholestasis	treatment	ISO	Nr1h4 (Rattus norvegicus)	mRNA:increased expression:liver (rat)	RGD
Nr1h4	Rat	extrahepatic cholestasis	treatment	IEP		mRNA:increased expression:liver (rat)	RGD
Nr1h4	Mouse	extrahepatic cholestasis	treatment	ISO	Nr1h4 (Rattus norvegicus)	mRNA:increased expression:liver (rat)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Abcc4 (ATP binding cassette subfamily C member 4)

Cyp27a1 (cytochrome P450, family 27, subfamily a, polypeptide 1)

Cyp7a1 (cytochrome P450 family 7 subfamily A member 1)

Cyp8b1 (cytochrome P450 family 8 subfamily B member 1)

Nr1h4 (nuclear receptor subfamily 1, group H, member 4)

Genes (Mus musculus)

Abcc4 (ATP-binding cassette, sub-family C member 4)

Cyp27a1 (cytochrome P450, family 27, subfamily a, polypeptide 1)

Cyp7a1 (cytochrome P450, family 7, subfamily a, polypeptide 1)

Cyp8b1 (cytochrome P450, family 8, subfamily b, 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))

CYP27A1 (cytochrome P450 family 27 subfamily A member 1)

CYP7A1 (cytochrome P450 family 7 subfamily A member 1)

CYP8B1 (cytochrome P450 family 8 subfamily B member 1)

NR1H4 (nuclear receptor subfamily 1 group H member 4)

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Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic acid against hepatotoxicity and cholestasis in bile duct ligation rats: involvement of SIRT1-mediated deacetylation of FXR and PGC-1α.