Preventive effect of ortho dimer of butylated hydroxyanisole on activator protein-1 activation and cyclooxygenase-2 expression in macrophages stimulated by fimbriae of Porphyromonas gingivalis, an oral anaerobe.

Abstract

Butylated hydroxyanisole (BHA; a mixture of 2- and 3-BHA) is widely used as a potent antioxidant, but is reported to have adverse effects, such as carcinogenesis and pro-inflammatory activity, possibly due to the pro-oxidant property of this compound. 2-Methoxyphenol dimers derived from ferulic acid were recently demonstrated to inhibit the expression of lipopolysaccharide-stimulated cyclooxygenase-2 (COX-2) via redox-sensitive transcription factors such as nuclear factor kappa B or activator protein-1 (AP-1), due to a weakening of its pro-oxidant property by dimerization. To develop anti-inflammatory and/or anticancer drugs for the prevention of oral diseases, such as leukoplakia and destructive chronic periodontitis, whether 2-BHA (2-tert-butyl-4-methoxyphenol) and its synthetic ortho dimer, bis-BHA (3,3'-di-tert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) can inhibit AP-1 transcriptional activity stimulated by Porphyromonas gingivalis fimbriae was examined. The fimbria-stimulated AP-1 activation of RAW 264.7 murine macrophages was markedly inhibited by bis-BHA. However, BHA showed slight inhibition. Furthermore, bis-BHA significantly inhibited fimbria-induced COX-2 gene expression, which is closely involved with inflammation and carcinogenesis. These findings suggest that bis-BHA may possess a potent anti-inflammatory effect against oral diseases.

• Authors: Yukio Murakami, Masao Shoji, Takako Ogiwara, Shoji Tanaka, Ichiro Yokoe, Seiichiro Fujisawa
• Journal: Anticancer research (Anticancer Res) 2006 Jul-Aug Vol. 26 Issue 4B Pg. 2915-20 ISSN: 0250-7005 [Print] Greece
• PMID: 16886613 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Cyclooxygenase 2 Inhibitors
• Transcription Factor AP-1
• Butylated Hydroxyanisole
• Cyclooxygenase 2

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Bacteroidaceae Infections (metabolism, microbiology)
• Butylated Hydroxyanisole (pharmacology)
• Cyclooxygenase 2 (biosynthesis)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dimerization
• Enzyme Induction (drug effects)
• Macrophages (drug effects, enzymology, metabolism, microbiology)
• Mice
• Mouth Diseases (metabolism, microbiology, prevention & control)
• Porphyromonas gingivalis (physiology)
• Transcription Factor AP-1 (antagonists & inhibitors, metabolism)
• Transcription, Genetic (drug effects)