Anti-inflammatory effect of caffeic acid methyl ester and its mode of action through the inhibition of prostaglandin E2, nitric oxide and tumor necrosis factor-alpha production.

Abstract	The anti-inflammatory effects of caffeic acid (CA), caffeic acid methyl ester (CM) and di-O-acetylcaffeic acid (DAC) were investigated in rats using the carrageenin-induced edema model and the antinociceptive effects of these compounds were also assessed in mice by means of the acetic acid-induced abdominal constriction test and hot plate test. CM (10mg/kg, p.o.) showed the most potent anti-inflammatory and antinociceptive effects in these animal models. To investigate the mechanism of the anti-inflammatory action, we examined the effects of these compounds on the lipopolysaccharide (LPS)-induced NO and PGE2 responses in the murine macrophage cell line, RAW 264.7. Our data indicate that CM is the most potent inhibitor of NO and PGE2 production and it also significantly decreased tumor necrosis factor-alpha (TNF-alpha) release. Consistent with these observations, the protein and mRNA expression levels of iNOS and COX-2 were found to be inhibited by CM in a dose-dependent manner. Furthermore, CM inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS, which was associated with the prevention of the degradation of the inhibitor kappaB, and subsequently with decreased p65 protein levels in the nucleus. Taken together, our data indicate that the anti-inflammatory properties of CM might result from the inhibition of iNOS, COX-2 and TNF-alpha expression through the down-regulation of NF-kappaB binding activity.
Authors	Kyung-Min Shin, In-Tae Kim, Young-Mi Park, Joohun Ha, Jong-Won Choi, Hee-Juhn Park, Yong Sup Lee, Kyung-Tae Lee
Journal	Biochemical pharmacology (Biochem Pharmacol) Vol. 68 Issue 12 Pg. 2327-36 (Dec 15 2004) ISSN: 0006-2952 [Print] England
PMID	15548379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Inflammatory Agents Caffeic Acids Carrier Proteins Esters I-kappa B Proteins Lipopolysaccharides NF-kappa B Neoplasm Proteins Nfkbia protein, mouse Nfkbia protein, rat Nucleocytoplasmic Transport Proteins Prostaglandins E RNA, Messenger Rela protein, mouse Transcription Factor RelA Tumor Necrosis Factor-alpha di-O-acetylcaffeic acid p65 oncofetal mRNA transport protein, rat NF-KappaB Inhibitor alpha Nitric Oxide Nitric Oxide Synthase Nitric Oxide Synthase Type II Nos2 protein, mouse Nos2 protein, rat Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases caffeic acid methyl ester caffeic acid
Topics	Active Transport, Cell Nucleus (drug effects) Animals Anti-Inflammatory Agents (pharmacology) Caffeic Acids (chemistry, pharmacology) Carrier Proteins (metabolism) Cells, Cultured Cyclooxygenase 2 Esters (pharmacology) I-kappa B Proteins (metabolism) Lipopolysaccharides Male Mice Mice, Inbred ICR NF-KappaB Inhibitor alpha NF-kappa B (metabolism) Neoplasm Proteins (metabolism) Nitric Oxide (metabolism) Nitric Oxide Synthase (biosynthesis, genetics) Nitric Oxide Synthase Type II Nucleocytoplasmic Transport Proteins (metabolism) Prostaglandin-Endoperoxide Synthases (biosynthesis, genetics) Prostaglandins E (metabolism) RNA, Messenger (metabolism) Rats Rats, Sprague-Dawley Transcription Factor RelA Tumor Necrosis Factor-alpha (metabolism)

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