| Title | Re-evaluation of cyclooxygenase-2-inhibiting activity of vanillin and guaiacol in macrophages stimulated with lipopolysaccharide. | | Author(s) | Murakami Y, Hirata A, Ito S, Shoji M, Tanaka S, Yasui T, Machino M, Fujisawa S | | Institution | Meikai University School of Dentistry, Sakado, Saitama 350-0283, Japan. ymura@dent.meikai.ac.jp | | Source | Anticancer Res 2007 Mar-Apr; 27(2):801-7. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 17465205 |
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