Protective effect of baicalin against lipopolysaccharide/D-galactosamine-induced liver injury in mice by up-regulation of heme oxygenase-1.

Abstract

Baicalin, a traditional anti-inflammatory drug, has been found to protect against liver injury in several experimental animal hepatitis models; however, the mechanisms underlying the hepatoprotective properties of baicalin are poorly understood. In the present study,we investigated the effects of baicalin on the acute liver injury in mice induced by Lipopolysaccharide/D-galactosamine (LPS/D-GalN). Baicalin (50, 150, and 300 mg/kg) was pretreated intraperitoneally (i.p.) at 2, 24, and 48 h respectively before LPS/D-GalN injected in mice. The mortality, hepatic tissue histology, hepatic tissue Tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO), plasma levels of TNF-alpha and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Besides, western blotting analyses of nuclear factor kappa B (NF-kappaB) translocation and Heme oxygenase-1(HO-1) protein expression, as well as HO-1 activity were determined. The results showed that baicalin protected against LPS/D-GalN-induced liver injury, including dose-dependent alleviation of mortality and hepatic pathological damage, decrease of ALT/AST release and the rise of MPO. Baicalin reduced nuclear translocation of NF-kappa B, TNF-alpha mRNA and protein levels in hepatic tissues and plasma levels of TNF-alpha induced by LPS/D-GalN. Moreover, baicalin dose-dependently increased HO-1 protein expression and activity. Further, inhibition of HO-1 activity significantly reversed the protective effect of baicalin against LPS/D-GalN-induced liver injury. These results suggest that baicalin can effectively prevent LPS/D-GalN-induced liver injury by inhibition of NF-kappa B activity to reduce TNF-alpha production and the underlying mechanism may be related to up-regulation of HO-1 protein and activity.

• Authors: Jing-Yuan Wan, Xia Gong, Li Zhang, Hong-Zhong Li, Yu-Fan Zhou, Qi-Xin Zhou
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 587 Issue 1-3 Pg. 302-8 (Jun 10 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18420187 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Flavonoids
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• baicalin
• Galactosamine
• Peroxidase
• Heme Oxygenase-1

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blotting, Western
• Chemical and Drug Induced Liver Injury (enzymology, pathology, prevention & control)
• Flavonoids (pharmacology)
• Galactosamine (antagonists & inhibitors, toxicity)
• Heme Oxygenase-1 (metabolism)
• Lipopolysaccharides (antagonists & inhibitors, toxicity)
• Liver (enzymology, pathology)
• Mice
• Mice, Inbred BALB C
• Peroxidase (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation (drug effects)