Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway.

Abstract

Emodin, 1,3,8-trihydroxy-6-methyl-anthraquinone, is an anthraquinone derivative from the roots of Rheum officinale Baill that has been used to treat many diseases in digestive system for thousands of years. This study is to disclose the mechanism of Emodin to treat cholestatic hepatitis via anti-inflammatory pathway. Rats were divided into Emodin, ursodeoxycholic acid, Dexamethasone, model and blank control groups with treatment of respective agent after administration of alpha-naphthylisothiocyanate. At 24 h, 48 h and 72 h time points after administration, liver function, pathological changes of hepatic tissue, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), cytokine-induced neutrophil chemoattractant (CINC)-1, macrophage inflammatory protein (MIP)-2, intercellular adhesion molecule (ICAM)-1, nuclear factor (NF)-kappaB and early growth response (Egr)-1, nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were detected. As a result, compared to the controls, Emodin had a notable effect on rat's living condition, pathological manifestation of hepatic tissue, total bilirubin, direct bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.05), but had little effect on alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) and total bile acid. With Emodin intervention, levels of TNF-alpha, IL-6, MPO, MDA, CINC-1, MIP-2, ICAM-1 and translocation of NF-kappaB were remarkably decreased, and levels of NO and iNOS were markedly increased (P<0.05). Emodin had no effect on Egr-1. In conclusion, Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis by anti-inflammation. The effects are mainly due to antagonizing pro-inflammatory cytokines and mediators, inhibiting oxidative damage, improving hepatic microcirculation, reducing impairment signals, and controlling neutrophil infiltration.

• Authors: Yan Ding, Lei Zhao, Hong Mei, Shu-Ling Zhang, Zhi-Hua Huang, Yan-Ying Duan, Pian Ye
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 590 Issue 1-3 Pg. 377-86 (Aug 20 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18590720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Early Growth Response Protein 1
• Egr1 protein, rat
• Interleukin-6
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Nitric Oxide
• Malondialdehyde
• 1-Naphthylisothiocyanate
• Peroxidase
• Nitric Oxide Synthase Type II
• Emodin

Topics

• 1-Naphthylisothiocyanate (toxicity)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Cholestasis (chemically induced, drug therapy, pathology, physiopathology)
• Early Growth Response Protein 1 (analysis)
• Emodin (therapeutic use)
• Hepatitis (drug therapy, pathology, physiopathology)
• Intercellular Adhesion Molecule-1 (analysis)
• Interleukin-6 (analysis)
• Liver (pathology, physiopathology)
• Male
• Malondialdehyde (analysis)
• Nitric Oxide (analysis)
• Nitric Oxide Synthase Type II (analysis)
• Peroxidase (analysis)
• Rats
• Rats, Sprague-Dawley
• Transcription Factor RelA (analysis)
• Tumor Necrosis Factor-alpha (analysis)