Comparative inhibitory effects of magnolol, honokiol, eugenol and bis-eugenol on cyclooxygenase-2 expression and nuclear factor-kappa B activation in RAW264.7 macrophage-like cells stimulated with fimbriae of Porphyromonas gingivalis

Autor: Yukio, Murakami, Akifumi, Kawata, Yuya, Seki, Teho, Koh, Kenji, Yuhara, Takehisa, Maruyama, Mamoru, Machino, Shigeru, Ito, Yoshinori, Kadoma, Seiichiro, Fujisawa
Rok vydání: 2012
Předmět:
Zdroj: In vivo (Athens, Greece). 26(6)
ISSN: 1791-7549
Popis: The anti-inflammatory activity of magnolol and related compounds is currently a focus of interest. In the present study, the inhibitory effects of these compounds on cyclooxygenase (COX-2) expression and nuclear factor-kappa B (NF-κB) activation were investigated in RAW264.7 macrophage-like cells stimulated with the fimbriae of Porphyromonas gingivalis, an oral anaerobe.The cytotoxicity of magnolol, honokiol, eugenol and bis-eugenol against RAW264.7 cells was determined using a cell counting kit (CCK-8). The regulatory effect of these compounds on the expression of COX-2 mRNA, stimulated by exposure to the fimbriae was investigated by real-time polymerase chain reaction (PCR). NF-κB activation was evaluated by enzyme-linked immunosorbent assay (ELISA)-like microwell colorimetric transcription factor activity assay (Trans-AM) and western blot analysis. The radical-scavenging activity was determined using the induction period method in the methyl methacrylate-azobisisobutyronitrile (AIBN) polymerization system under nearly anaerobic conditions. The phenolic bond dissociation enthalpy (BDE) and orbital energy were calculated at the density functional theory (DFT) B3LYP/6-31G* level.The cytotoxicity against RAW264.7 cells declined in the order bis-eugenoleugenolhonokiolmagnolol, whereas the radical-scavenging activity declined in the order honokiol, bis-eugenolmagnololeugenol. Magnolol and honokiol significantly inhibited the fimbria-induced expression of COX-2 at non-cytotoxic concentrations. Both the fimbria-stimulated binding of NF-κB to its consensus sequence and phosphorylation-dependent proteolysis of inhibitor κB-α were markedly inhibited by magnilol and honokiol, whereas eugenol and bis-eugenol did not inhibit COX-2 expression and NF-κB activation. Magnolol and honokiol possessed a high electronegativity (χ) value.Magnolol and honokiol exhibit antioxidative activity, low cytotoxicity, and anti-inflammatory activity. These compounds may be capable of preventing chronic inflammatory diseases induced by oral bacteria.
Databáze: OpenAIRE