TY - JOUR T1 - Inhibitory Effects of <em>p</em>-Cresol and <em>p</em>-Hydroxy Anisole Dimers on Expression of the Cyclooxygenase-2 Gene and Lipopolysaccharide-stimulated Activation of Nuclear Factor-κB in RAW264.7 Cells JF - In Vivo JO - In Vivo SP - 719 LP - 725 VL - 28 IS - 5 AU - YUKIO MURAKAMI AU - AKIFUMI KAWATA AU - SHIGERU ITO AU - TADASHI KATAYAMA AU - SEIICHIRO FUJISAWA Y1 - 2014/09/01 UR - http://iv.iiarjournals.org/content/28/5/719.abstract N2 - Background/Aim: Phenolic compounds, particularly dihydroxybiphenyl-related compounds, possess efficient anti-oxidative and anti-inflammatory activity. We investigated the anti-inflammatory activity of 2,2’-dihydroxy-5,5’-dimethylbiphenol (p-cresol dimer), 2,2’-dihydroxy-5,5’-dimethoxybiphenol (pHA dimer), p-cresol, p-hydroxyanisole (pHA) and 2-t-butyl-4-hydroxyanisole (BHA). Materials and Methods: The cytotoxicity of the investigated compounds against RAW264.7 cells was determined using a cell counting kit (CCK-8). Their inhibitory effects on cyclooxygenase-2 (Cox2) mRNA expression stimulated by lipopolysaccharide (LPS) were determined using northern blot analysis, and their inhibition of LPS-stimulated nuclear factor-kappa B (Nf-κb) activation was evaluated using enzyme-linked immunosorbent assay-like microwell colorimetric transcription factor activity assay. The molecular orbital energy was calculated on the basis of density function theory BLYP/6-31G*. Results: The cytotoxicity of the compounds declined in the order pHA dimer &gt; p-cresol dimer &gt; BHA &gt; p-cresol &gt; pHA. The inhibitory effect on Cox2 expression and Nf-κb activation was enhanced by p-cresol dimer and pHA dimer, particularly the former, suggesting potent anti-inflammatory activity, whereas p-cresol and pHA showed weak activity, and BHA no activity. Both p-cresol dimer and pHA dimer were highly electronegative, as determined by quantum chemical calculations. Conclusion: Dimerization of p-cresol and pHA enhances their anti-inflammatory activity. p-Cresol dimer and pHA dimer, particularly the former, are potent anti-inflammatory agents. ER -