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.
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.
Murakami
Yukio
Y
Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado City, Saitama, Japan. ymura@dent.meikai.ac.jp
Shoji
Masao
M
Ogiwara
Takako
T
Tanaka
Shoji
S
Yokoe
Ichiro
I
Fujisawa
Seiichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016866:Bacteroidaceae Infections / Q000378:metabolism / Q000382:microbiology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D019281:Dimerization; D004790:Enzyme Induction / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D009059:Mouth Diseases / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D016966:Porphyromonas gingivalis / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D018808:Transcription Factor AP-1; D002083:Butylated Hydroxyanisole; D051546:Cyclooxygenase 2