Effect and mechanism of emodin on cholestatic hepatitis.
- Author:
Yan DING
1
;
Lei ZHAO
;
Hong MEI
;
Han-ming PENG
;
Yuan GAO
;
Zhi-hua HUANG
;
Shi-xiu KANG
Author Information
- Publication Type:Journal Article
- MeSH: 1-Naphthylisothiocyanate; Animals; Anti-Inflammatory Agents; pharmacology; therapeutic use; Chemical and Drug Induced Liver Injury; drug therapy; metabolism; Cholestasis, Intrahepatic; chemically induced; drug therapy; metabolism; Early Growth Response Protein 1; genetics; metabolism; Emodin; pharmacology; therapeutic use; Immunohistochemistry; Intercellular Adhesion Molecule-1; metabolism; Interleukin-6; metabolism; Liver; metabolism; pathology; Liver Function Tests; Male; NF-kappa B; metabolism; RNA, Messenger; genetics; metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha; metabolism
- From: Chinese Journal of Hepatology 2009;17(5):368-373
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo explore the therapeutic effect and mechanism of emodin on cholestatic hepatitis.
METHODSRats were divided into 5 groups: 1 group was untreated, the other 4 groups were treated with alpha-naphthylisothiocyanate (ANIT), ANIT and emodin, ANIT and ursodeoxycholic acid, or ANIT and dexamethasone, respectively. At 24 h, 48 h and 72 h after the treatment, NF-kappa B, early growth response factor-1 (Egr-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), macrophage inflammatory protein 2 (MIP-2), intercellular adhesion molecule 1 (ICAM-1),tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) were assayed by immunohistochemistry, real-time PCR , western-blot and ELISA. The level of malondialdehyde (MDA), superoxide Dismutase(SOD) and myeloperoxidase (MPO) were assayed by thiobarbituric acid method, xanthine oxidase method and colorimetric method, respectively.
RESULTS(1) Compared to the controls, emodin had a notable effect on total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT) at all time points (all P less than 0.05). Compared to ursodeoxycholic acid, emodin had a notable effect on TB and DB at 24 h after the treatments, however, after 48 h, emodin had a notable effect only on TB (all P less than 0.05). Compared to Dexamethasone, emodin had a notable effect on TB at 48 h time point, and it had a notable effect on ALT at all time points (all P less than 0.05). (2) The nuclei NF-kappa B p65 staining was significantly increased at 24 h and 48 h after ANIT treatment (all P less than 0.05), and emodin treatment could block the increase (all P less than 0.05). (3) Egr-1 mRNA level was not affected by emodin treatment (P more than 0.05); levels of CINC-1, MIP-2 mRNA and ICAM-1 protein were significantly decreased after emodin treatment (all P less than 0.05). (4) The levels of TNF alpha and IL-6 were decreased after emodin treatment(all P less than 0.05). (5) The levels of MDA at all time points and MPO at 24 h, 48 h time points were notably down-regulated by emodin treatment, while the level of SOD was markedly elevated at all time points after emodin treatment (all P less than 0.05).
CONCLUSIONSEmodin treatment can reduce the levels of TB, DB and ALT in ANIT induced-cholestatic hepatitis. The effect may be due to inhibition of NF-kappa B signal pathway.
