How does emodin protect rat liver from fibrogenesis?

In the last decade, advances in the understanding of genes promoting hepatic stellate cell (HSC) activation are impressive. However, there are few breakthroughs in therapeutic intervention of hepatic fibrogenesis. Efficient and well-tolerated antifibrotic drugs are lacking and current treatment of hepatic fibrosis is limited to withdrawal of the noxious agent. Research identifying innocuous antifibrotic agents is of high priority and urgently needed. Emodin is efficacious in the management of hepatic fibrosis. However, the mechanisms underlying its effects remain to be elucidated.

A research team from China established rat models of experimental hepatic fibrosis by injection with CCl4; the treated rats received emodin via oral administration at a dosage of 20 mg/kg twice a week at the same time. Rats injected with olive oil served as a normal group. Histopathological changes were observed by hematoxylin and eosin staining. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and hepatic hydroxyproline content were assayed by biochemical analyses. The mRNA and protein relevant to hepatic stellate cell (HSC) activation in the liver were assessed using real-time reverse transcription-polymerase chain reaction, immunohistochemistry, western blotting and enzyme-linked immunosorbent assay. Their study will be published on October 14, 2009 in the World Journal of Gastroenterology.

The results showed that the degree of hepatic fibrosis increased markedly in the CCl4 group compared to the normal group, and decreased markedly in the emodin group compared to the CCl4 group according to METAVIR scale compared with those in the normal control group. The activities of serum ALT and AST were significantly higher in rats injected with CCl4. The activities of serum ALT and AST were significantly reduced by administration of emodin. Compared with the normal controls, hepatic hydroxyproline content was significantly higher in rats injected with CCl4. Hepatic hydroxyproline content was significantly reduced in the rats treated with emodin at 20 mg/kg. Emodin significantly protected the liver from injury by reducing serum AST and ALT activities and reducing hepatic hydroxyproline content. The mRNA levels of transforming growth factor-b1 (TGF-b1), Smad4 and a-SMA in liver tissues were significantly down-regulated in SD rats that received emodin treatment. Furthermore, significant down-regulation of serum TGF-b1 protein levels and protein expression of Smad4 and a-SMA in liver tissues was also observed in the rats. Emodin inhibited HSC activation by reducing the abundance of TGF-b1 and Smad4.

The researchers drew a conclusion that emodin is active as an antifibrogenic drug to reduce the biological effects of TGF-b1 in ongoing fibrogenesis. Emodin, the main active monomer isolated from Giant Knotweed Rhizome, may be an attractive therapeutic agent for the treatment of fibrotic liver diseases.

Reference: Dong MX, Jia Y, Zhang YB, Li CC, Geng YT, Zhou L, Li XY, Liu JC, Niu YC. Emodin protects rat liver from CCl4-induced fibrogenesis via inhibition of hepatic stellate cells activation. World J Gastroenterol 2009; 15(38): 4753-4762

http://www.wjgnet.com/1007-9327/15/4753.asp

Correspondence to: Dr. Ying-Cai Niu, The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar, 161006, Heilongjiang Province, China. nyc1968@sohu.com

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World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H. pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2008 IF: 2.081. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.