Abstract Objective To investigate the expression of farnesoid X receptor (FXR) and the effect of emodin on FXR expression in a rat model of acute cholestatic hepatitis. Methods Ninety adult Sprague-Dawley rats were randomly divided into normal control, model, and emodin groups (n=30 each). The model and emodin groups were given alpha-naphthylisothiocyanate (ANIT) 50 mg/kg by gavage to establish an animal model of cholestatic hepatitis, while the normal control group was given an equal volume of sesame oil. The emodin group was given emodin by gavage every day from 4 days before the model was prepared until the time of sacrifice, while the model and normal control groups were given an equal volume of sodium carboxymethyl cellulose solution. At 24, 48 and 72 hours after the model was prepared, serum level of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), and total bile acids (TBA) were measured by Aeroset automatic biochemical analyzer, and the mRNA expression of FXR in the liver tissue was measured by real-time PCR. Results At all time points FXR mRNA expression in the model group decreased, but serum levels of TB, DB, ALT and TBA increased significantly compared with the normal control group (PPConclusions Emodin can significantly reduce serum levels of TB, DB, ALT, and TBA in rats with ANIT-induced cholestatic hepatitis, probably by promoting FXR expression.
DING Yan,XU Fang,XIONG Xiao-Li et al. Effect of emodin on expression of farnesoid X receptor in rats with acute cholestatic hepatitis[J]. CJCP, 2014, 16(4): 424-429.
DING Yan,XU Fang,XIONG Xiao-Li et al. Effect of emodin on expression of farnesoid X receptor in rats with acute cholestatic hepatitis[J]. CJCP, 2014, 16(4): 424-429.
Ding Y, Zhao L, Mei H, et al. Alterations of biliary biochemical constituents and cytokines in infantile hepatitis syndrome[J]. World J Gastroenterol, 2006, 12(43): 7038-7041.
Poupon R. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action[J]. Clin Res Hepatol Gastroenterol, 2012, 36(Suppl 1): S3-S12.
[6]
Li HL, Chen HL, Li H, et al. Regulatory effects of emodin on NF-kappaB activation and inflammatory cytokine expression in RAW 264.7 macrophages[J]. Int J Mol Med, 2005, 16(1): 41-47.
[7]
Koyama J, Inoue M, Morita I, et al. Correlation between reduction potentials and inhibitory effects on Epstein-Barr virus activation by emodin derivatives[J]. Cancer Lett, 2006, 241(2): 263-267.
[8]
Ho TY, Wu SL, Chen JC, et al. modin blocks the SARS coranavirus spike protein and angiotension-converting enzyme 2 interaction[J]. Antiviral Res, 2007, 74(2): 92-101.
[9]
Ghosh S, Das Sarma M, Patra A, et al. Anti-inflammatory and anticancer compounds isolated from Ventilago madraspatana Gaertn, Rubia cordifolia Linn and Lantana camara Linn[J]. J Pharm Pharmacol, 2010, 62(9): 1158-1166.
[10]
Zhang HQ, Zhou CH, Wu YQ. Effect of emodin on small intestinal peristalsis of mice and relevant mechanism[J]. World J Gastroenterol, 2005, 11(20): 3147-3150.
[11]
Ding Y, Zhao L, Mei H, et al. Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway[J]. Eur J Pharmacol, 2008, 590(1-3): 377-386.
[12]
Sturm E, Wagner M, Trauner M. Nuclear receptor ligands in therapy of cholestatic liver disease[J]. Front Biosci, 2009, 14: 4299-4325.
[13]
Goldfarb S, Singer EJ, Popper H. Experimental cholangitis due to alpha-naphthylisothiocyanate(ANIT)[J]. Am J Pathol, 1962, 40: 685-698.
[14]
Hillstrom J, Duane WC, Eckfeldt JH, et al. Lack of benefit of ursodeoxycholic acid in drug-induced cholestasis in the rat[J]. Proc Soc Exp Biol Med, 1992, 200(1): 122-126.
[15]
Carey EJ, Lindor KD. Current pharmacotherapy for cholestatic liver disease[J]. Expert Opin Pharmacother, 2012, 13(17): 2473-2484.
[16]
Wang YD, Chen WD, Moore DD, et al. FXR: a metabolic regulator and cell protector[J]. Cell Res, 2008, 18(11): 1087-1095.
[17]
Fiorucci S, Mencarelli A, Distrutti E, et al. Targetting farnesoid-X-receptor: from medicinal chemistry to disease treatment[J]. Curr Med Chem, 2010, 17(2): 139-159.
[18]
Zhang Y, Edwards PA. FXR signaling in metabolic disease[J]. FEBS Lett, 2008, 582(1): 10-18.
[19]
Zollner G, Trauner M. Nuclear receptors as therapeutic targets in cholestatic liver diseases[J]. Br J Pharmacol, 2009, 156(1): 7-27.
