[Therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof: experiment with rats].
OBJECTIVE
To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof.


METHODS
96 SD rats were randomly divided into 4 groups to be treated with emodin, ursodeoxycholic acid, dexamethasone, or normal saline respectively for 4 days. On the 5th day gastric perfusion of alpha-naphthylisothiocyanate (ANIT) was performed to establish models of cholestatic hepatitis. 4 - 6 hours after the establishment of model the above mentioned agents were given continuously. 24, 48, and 72 hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), and total bile acid (TBA). Specimen of liver was collected to undergo pathological examination. PCR was used to detect the mRNA expression of cytokine-induced neutrophil chemoattractant 1 (CINC-1) and macrophage inflammatory protein 2(MIP-2), and Western blotting was used to detect the protein expression of intercellular adhesion molecule 1 (ICAM-1). Twenty-four rats treated with NS only were used as controls.


RESULTS
The pathological changes of behaviors and liver of the emodin and ursodeoxycholic acid groups were all remarkably milder than those of other model groups. The levels of TB [(32.8 +/- 3.7) micromol/L, (61.0 +/- 16.4) micromol/L, (10.8 +/- 4.5) micromol/L], DB[ (26.03 +/- 3.10) micromol/L, (49.40 +/- 18.16) micromol/L, (8.04 +/- 3.03) micromol/L], and ALT [(314 +/- 50) U/L, (664 +/- 97) U/L, (200 +/- 60) U/L], at the time points 24, 48, and 72 hours, the 48 and 72 hours AST levels, the 48 hours ALP level, the 72 hours GGT level, and the 48 and 72 hours TBA levels of the emodin group were all significantly lower than those of the model group (all P < 0.05). The 24 and 48 hours TB levels, 24 hours DB and ALT, and 24, 72 hours TBA levels of the emodin group were all significantly lower than those of the ursodeoxycholic acid group (all P < 0.05). The 24, 48 hours TB and TBA levels, and the ALT, AST and GGT levels at all time points of the emodin group were all significantly lower than those of the dexamethasone group (all P < 0.05). The CINC-1 and MIP-2 mRNA expression levels and ICAM-1 protein expression levels at all time points of the emodin group were all significantly lower than those of the model group (all P < 0.05).


CONCLUSIONS
Decreasing the levels of TB, DB and ALT in particular, emodin has a protective effect on cholestatic hepatitis. Its effects are quicker than ursodeoxycholic acid, and it has better effects on ALT, AST GGT, and TBA than dexamethasone. These effects may be due to inhibition of the activation of CINC-1, MIP-2, and ICAM-1.
Ding
Yan
Y
Department of Gastroenterology and Hepatology, Medical and Health Center for Women and Children, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China. dingyanmx@163.com
Zhao
Lei
L
Huang
Zhi-Hua
ZH
Mei
Hong
H
Dong
Hai-Feng
HF
Dong
Ji-Hua
JH
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2; D002779:Cholestasis / Q000150:complications; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D004642:Emodin / Q000627:therapeutic use*; D006505:Hepatitis / Q000188:drug therapy* / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C513297:Cxcl1 protein, rat; D004365:Drugs, Chinese Herbal; D018799:Intercellular Adhesion Molecule-1; D000410:Alanine Transaminase; D004642:Emodin; D001663:Bilirubin