4-O-Methylgallic acid suppresses inflammation-associated gene expression by inhibition of redox-based NF-kappaB activation.

Abstract

4-O-methylgallic acid (4-OMGA) is an in vivo major metabolite of gallic acid which is abundant in red wine, tea, legumes and fruit. We examined the in vitro and in vivo effects of 4-OMGA on the production and expression of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) as well as the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). 4-OMGA inhibited the expression and production of these inflammatory genes and mediators in RAW264.7 cells and primary macrophages stimulated with lipopolysaccharide (LPS). This compound also reduced the serum levels of these inflammatory mediators in endotoxemic mice. 4-OMGA inhibited iNOS promoter activity and NF-kappaB activation in LPS-treated RAW264.7 cells. 4-OMGA inhibited the LPS-mediated increase in reactive oxygen species production and exogenous H(2)O(2)-induced NF-kappaB activation. Moreover, this compound blocked IkappaBalpha phosphorylation and degradation and nuclear translocation of the cytosolic NF-kappaB p65 subunit, which highly correlated with its inhibitory effect on IkappaB kinase activity and inflammatory mediator production. These results suggest that 4-OMGA suppresses inflammation-associated gene expression by blocking NF-kappaB activation through the inhibition of redox-sensitive IkappaB kinase activity, suggesting that this compound may be beneficial for treating endotoxemia.

• Authors: Hee-Jun Na, Gwangsoo Lee, Heung-Young Oh, Ki-Suk Jeon, Ho-Jeong Kwon, Kwon-Soo Ha, Hansoo Lee, Young-Guen Kwon, Young-Myeong Kim
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 6 Issue 10 Pg. 1597-608 (Oct 2006) ISSN: 1567-5769 [Print] Netherlands
• PMID: 16919832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• NF-kappa B
• Reactive Oxygen Species
• 3,5-dihydroxy-4-methoxybenzoic acid
• Gallic Acid

Topics

• Animals
• Cell Line
• Endotoxemia (drug therapy, genetics, immunology)
• Enzyme-Linked Immunosorbent Assay
• Gallic Acid (analogs & derivatives, pharmacology)
• Gene Expression (drug effects, immunology)
• Inflammation Mediators (immunology, metabolism)
• Macrophages (drug effects, immunology, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• NF-kappa B (antagonists & inhibitors, immunology)
• Oxidation-Reduction
• Reactive Oxygen Species (metabolism)