RRC ID 42961
Author Murakami Y, Hirata A, Ito S, Shoji M, Tanaka S, Yasui T, Machino M, Fujisawa S.
Title Re-evaluation of cyclooxygenase-2-inhibiting activity of vanillin and guaiacol in macrophages stimulated with lipopolysaccharide.
Journal Anticancer Res
Abstract Phytophenols such as para-substituted 2-methoxyphenols exhibit antioxidant and anti-inflammatory activities, however, their biological activities are concentration-dependent, possibly due to their dual property of being both antioxidant and prooxidant. Eugenol (2-allyl-2-methoxyphenol) and isoeugenol (4-propenyl-2-methoxyphenol) did not reveal cyclooxygenase-2 (COX-2)-inhibiting activity in macrophages stimulated with lipopolysaccharide (LPS). In contrast, vanillin (2-hydroxy-3-methoxybenzaldehyde) and guaiacol (2-methoxyphenol), especially the former, inhibited LPS-stimulated nuclear factor kappa B (NF-kappaB) activation and cyclooxygenase (COX)-2 gene expression in cells of the RAW 264.7 murine macrophage cell line. Among the 2-methoxyphenols, vanillin demonstrated a potent anti-inflammatory activity. The phenolic O-H bond dissociation enthalpy (BDE) and molecular orbital energies (chemical hardness [eta], electronegativity [chi], and electrophilicity [omega]) were examined to clarify the mechanism responsible for inhibition of COX-2 expression. The BDE, chi, and omega values for vanillin were significantly higher than the corresponding values for the other 2-methoxyphenols. The anti-inflammatory activity of 2-methoxyphenols depended on the BDE and the phenol function was crucial for eliciting this activity. In addition, the anti-inflammatory activity depended on the chi and omega. These findings make vanillin attractive as a candidate therapeutic agent.
Volume 27(2)
Pages 801-7
Published 2007-3
PMID 17465205
MeSH Animals Benzaldehydes / pharmacology* Blotting, Northern Blotting, Western Cell Line Cyclooxygenase 2 / biosynthesis Cyclooxygenase 2 / metabolism Cyclooxygenase 2 Inhibitors / pharmacology* Drug Interactions Guaiacol / pharmacology* Lipopolysaccharides / antagonists & inhibitors Lipopolysaccharides / pharmacology* Macrophages / drug effects Macrophages / enzymology Mice NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism Phosphorylation
IF 1.935
Times Cited 49
Human and Animal Cells