PT  - JOURNAL ARTICLE
AU  - YUKIO MURAKAMI
AU  - ATSUSHI HIRATA
AU  - SHIGERU ITO
AU  - MASAO SHOJI
AU  - SHOJI TANAKA
AU  - TOSHIKAZU YASUI
AU  - MAMORU MACHINO
AU  - SEIICHIRO FUJISAWA
TI  - Re-evaluation of Cyclooxygenase-2-inhibiting Activity of Vanillin and Guaiacol in Macrophages Stimulated with Lipopolysaccharide
DP  - 2007 Mar 01
TA  - Anticancer Research
PG  - 801--807
VI  - 27
IP  - 2
4099  - http://ar.iiarjournals.org/content/27/2/801.short
4100  - http://ar.iiarjournals.org/content/27/2/801.full
SO  - Anticancer Res2007 Mar 01; 27
AB  - 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-κB) 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. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved