Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway.

Abstract

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl(4)) induced hepatotoxicity have not been clarified. The aim of the present study was to investigate the effects of UA on oxidative stress and inflammation in liver of CCl(4) treated mice. Male ICR mice were injected with CCl(4) with or without UA co-administration (25 and 50 mg/kg intragastrically once daily) for one week. Our data showed that UA significantly prevented CCl(4)-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl(4)-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) level in liver, were suppressed by treatment with UA. Furthermore, western blot analysis showed that UA significantly decreased CYP2E1 expression levels and production of pro-inflammatory markers including TNF-α, IL-1β and COX-2 in CCl(4)-treated mouse liver. In exploring the underlying mechanisms of UA action, we found that UA decreased the activation of mitogen-activated protein kinases (JNK, p38 MAPK, ERK), which in turn inactivated the immunoregulatory transcription factor nuclear factor kappa B (NF-κB) in liver of CCl(4) treated mice. In conclusion, these results suggested that the inhibition of CCl(4)-induced inflammation by UA is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-κB signaling pathway.

• Authors: Jie-Qiong Ma, Jie Ding, Li Zhang, Chan-Min Liu
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 37 Issue 3 Pg. 975-83 (May 2014) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 24727148 (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
• Antioxidants
• Interleukin-6
• NF-kappa B
• Reactive Oxygen Species
• Thiobarbituric Acid Reactive Substances
• Triterpenes
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Carbon Tetrachloride
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Aspartate Aminotransferases
• Alanine Transaminase
• Mitogen-Activated Protein Kinases
• ursolic acid

Topics

• Alanine Transaminase (blood)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Aspartate Aminotransferases (blood)
• Carbon Tetrachloride
• Chemical and Drug Induced Liver Injury (metabolism, pathology, prevention & control)
• Cyclooxygenase 2 (metabolism)
• Interleukin-6 (metabolism)
• Liver (drug effects, metabolism, pathology)
• Male
• Mice, Inbred ICR
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Thiobarbituric Acid Reactive Substances (metabolism)
• Triterpenes (pharmacology)
• Tumor Necrosis Factor-alpha (metabolism)