[Effect and mechanism of emodin on cholestatic hepatitis]

Zhonghua Gan Zang Bing Za Zhi. 2009 May;17(5):368-73.
[Article in Chinese]

Abstract

Objective: To explore the therapeutic effect and mechanism of emodin on cholestatic hepatitis.

Methods: Rats 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).

Conclusions: Emodin 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Naphthylisothiocyanate
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism
  • Cholestasis, Intrahepatic / chemically induced
  • Cholestasis, Intrahepatic / drug therapy*
  • Cholestasis, Intrahepatic / metabolism
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism
  • Emodin / pharmacology*
  • Emodin / therapeutic use
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-6 / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Function Tests
  • Male
  • NF-kappa B / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Early Growth Response Protein 1
  • Interleukin-6
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • 1-Naphthylisothiocyanate
  • Emodin