Protective effect of tormentic acid from Potentilla chinensis against lipopolysaccharide/D-galactosamine induced fulminant hepatic failure in mice.

Abstract

A compound was isolated from Potentilla chinensis, and it was identified as tormentic acid (TA) based on its physicochemical properties and spectral data. The hepatoprotective effect of TA was evaluated using an acute liver failure model induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN). The results revealed that TA significantly prevented LPS/D-GalN-induced fulminant hepatic failure, as evidenced by the decrease in serum aminotransferase and total bilirubin activities and the attenuation of histopathological changes. TA alleviated the pro-inflammatory cytokines including TNF-α and NO/iNOS by inhibiting nuclear factor-κB (NF-κB) activity. Moreover, TA strongly inhibited lipid peroxidation, recruited the anti-oxidative defense system, and increased HO-1 activity. In addition, TA significantly attenuated increases in TUNEL-positive hepatocytes through decreasing the levels of cytochrome c, as well as caspases-3, 8 and 9, while augmenting the expression of Bcl-2. In conclusion, TA protects hepatocytes against LPS/D-GalN-induced injury by blocking NF-κB signaling pathway for anti-inflammatory response and attenuating hepatocellular apoptosis. Consequently, TA is a potential agent for preventing acute liver injury and may be a major bioactive ingredient of Potentilla chinensis.

• Authors: Xing Lin, Shijun Zhang, Renbin Huang, Shimei Tan, Shuang Liang, Xiaoyan Wu, Lang Zhuo, Quanfang Huang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 19 Issue 2 Pg. 365-72 (Apr 2014) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24560903 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• Membrane Proteins
• Protective Agents
• Proto-Oncogene Proteins c-bcl-2
• Transcription Factor RelA
• Triterpenes
• euscaphic acid
• Galactosamine
• Cytochromes c
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Caspases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Caspases (metabolism)
• Cytochromes c (metabolism)
• Cytokines (blood, genetics)
• Galactosamine
• Heme Oxygenase-1 (metabolism)
• Lipid Peroxidation (drug effects)
• Lipopolysaccharides
• Liver (drug effects, metabolism, pathology)
• Liver Failure, Acute (chemically induced, drug therapy, metabolism, pathology)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Nitric Oxide Synthase Type II (genetics)
• Phytotherapy
• Potentilla
• Protective Agents (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Transcription Factor RelA (metabolism)
• Triterpenes (pharmacology, therapeutic use)