Format

Send to

Choose Destination
J Hepatobiliary Pancreat Sci. 2018 Mar;25(3):195-205. doi: 10.1002/jhbp.537.

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.

Author information

1
Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
2
Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
3
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian 116011, China.
4
Department of Gastrointestinal Endoscopy, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
5
Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
6
Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, China.

Abstract

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.

KEYWORDS:

Chlorogenic acid; Cholestasis; Farnesoid X receptor; Hepatotoxicity; Peroxisome proliferator-activated receptor γ coactivator 1-α; Sirtuin 1

PMID:
29360226
DOI:
10.1002/jhbp.537
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center