Ethanol extract from Artemisia vestita, a traditional Tibetan medicine, exerts anti-sepsis action through down-regulating the MAPK and NF-kappaB pathways.

Abstract

Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical application for inflammatory diseases. However, its molecular mechanism of anti-inflammatory effect is poorly understood. In the present study, we investigated the anti-inflammatory activity and underlying mechanism of the ethanol extract from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis. Pretreatment with AV-ext significantly decreased the levels of tumor necrosis factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the survival of mice with experimental sepsis. AV-ext also remarkably reduced the expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS-stimulated RAW 264.7 macrophages and dose dependently suppressed the activation of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal-regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore, pretreatment with AV-ext dose dependently inhibited the activation of nuclear factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be beneficial for the treatment of endotoxin shock or sepsis.

• Authors: Yang Sun, Yi-Hua Li, Xing-Xin Wu, Wei Zheng, Zong-Hui Guo, Yang Li, Ting Chen, Zi-Chun Hua, Qiang Xu
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 17 Issue 5 Pg. 957-62 (May 2006) ISSN: 1107-3756 [Print] Greece
• PMID: 16596287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• I-kappa B Proteins
• Interleukin-1
• Lipopolysaccharides
• NF-kappa B
• Nfkbia protein, mouse
• Plant Extracts
• Tumor Necrosis Factor-alpha
• NF-KappaB Inhibitor alpha
• Ethanol
• Cyclooxygenase 2
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Artemisia (chemistry)
• Cell Line
• Cyclooxygenase 2 (metabolism)
• Down-Regulation (drug effects)
• Ethanol (chemistry)
• Gene Expression (drug effects)
• I-kappa B Proteins (metabolism)
• Interleukin-1 (metabolism)
• Lipopolysaccharides (administration & dosage, toxicity)
• Macrophages, Peritoneal (cytology, drug effects, metabolism)
• Male
• Medicine, Tibetan Traditional
• Mice
• Mice, Inbred BALB C
• Mitogen-Activated Protein Kinases (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Phytotherapy
• Plant Extracts (isolation & purification, pharmacology)
• Sepsis (metabolism, mortality, prevention & control)
• Signal Transduction (drug effects)
• Specific Pathogen-Free Organisms
• Tumor Necrosis Factor-alpha (genetics, metabolism)