Effect of oxymatrine on the p38 mitogen-activated protein kinases signalling pathway in rats with CCl4 induced hepatic fibrosis.

Abstract

BACKGROUND:

Recent studies have suggested that p38 mitogen-activated protein kinases (MAPK) signalling pathway plays an important role in hepatic fibrosis. This study explored the antifibrotic effect of oxymatrine on tetrachloromethane induced liver fibrosis in rats and its modulation on the p38 MAPK signalling pathway.

METHODS:

One hundred and twenty healthy male Sprague-Dawley rats were randomly assigned to six groups: normal (n = 20), induced fibrosis (n = 20), colchicine (n = 20) and three treatment groups of oxymatrine (n = 20 x 3). We obesrved changes in deposition of collagen, hyaluronic acid (HA), laminin (LN), collagen type IV (CIV), procollagen III (PCIII) and hydroxyproline (Hyp), a-smooth muscle actin (alpha-SMA) and phosphor-p38 (pp38).

RESULTS:

The relative indicators of changes in histopathology, HA, LN, CIV, PCIII, Hyp, alpha-SMA and pp38 were raised significantly in the induced fibrosis group (P < 0.01 vs normal group). The semiquantitative hepatic fibrosis staging scores of middle dose group and high dose group were decreased (P < 0.05 and P < 0.01 respectively vs the induced fibrosis group), as was the average area of collagen in rats' liver, the concentrations of serum HA, LN, CIV, PCIII and liver tissue homogenate Hyp. The gene expression of alpha-SMA mRNA was considerably decreased in the treated animals, as was the protein espression of pp38 protein.

CONCLUSIONS:

Oxymatrine is effective in reducing the production and deposition of collagen in the liver tissue of experimental rats in ways which relate to modulating the fibrogenic signal transduction via p38 MAPK signalling pathway.

• Authors: Zi-Yu Deng, Jun Li, Yong Jin, Xiao-Liang Chen, Xiong-Wen Lü
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 122 Issue 12 Pg. 1449-54 (Jun 20 2009) ISSN: 2542-5641 [Electronic] China
• PMID: 19567170 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Actins
• Alkaloids
• Anti-Arrhythmia Agents
• Collagen Type IV
• Laminin
• Procollagen
• Quinolizines
• oxymatrine
• Hyaluronic Acid
• Collagen
• Carbon Tetrachloride
• p38 Mitogen-Activated Protein Kinases
• Hydroxyproline

Topics

• Actins (metabolism)
• Alkaloids (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Carbon Tetrachloride
• Collagen (metabolism)
• Collagen Type IV (metabolism)
• Hyaluronic Acid (metabolism)
• Hydroxyproline (metabolism)
• Laminin (metabolism)
• Liver Cirrhosis (chemically induced, drug therapy, metabolism)
• Male
• Procollagen (metabolism)
• Quinolizines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)