Comparative anti-inflammatory activities of curcumin and tetrahydrocurcumin based on the phenolic O-H bond dissociation enthalpy, ionization potential and quantum chemical descriptor.
Curcumin and its reduced derivative tetrahydrocurcumin have been shown to exhibit chemopreventive activity. Cyclooxygenase-2 (COX-2) inhibition in lipopolysaccharide (LPS)- or Porphyromonas gingivalis fimbria-stimulated RAW 264.7 cells was investigated using Northern blot analysis. The fimbria-stimulated expression of the COX-2 gene was inhibited by curcumin but not by tetrahydrocurcumin. LPS-stimulated COX-2 gene expression was completely inhibited by curcumin, but an increase in the concentration of tetrahydrocurcumin did not cause complete inhibition of COX-2 expression. The inhibitory effect of curcumin on nuclear factor kappa B (NF-kappaB) activation in the cells was clearly observed, but that of tetrahydrocurcumin was incomplete even at a concentration of 20 microM. To explain the difference in effect between the two compounds, analysis of the frontier orbital was performed using ab initio 6-31G* wave function. The calculated chemical hardness (eta) for curcumin was clearly smaller, whereas its electronegativity (chi) and electrophilicity (omega) were clearly greater than the corresponding values for the curcumin-related compounds tetrahydrocurcumin, isoeugenol and eugenol. This suggested that the anti-inflammatory activities of curcumin may be related to eta-, chi- and/or omega-controlled enzymes. In addition, the bond dissociation enthalpy (BDE) of the phenolic OH was calculated using the density function theory (DFT)/B3LY. The total BDE values of curcumin and tetrahydrocurcumin were almost identical, but the BDE of one-electron oxidation and ionization potential (IP) for curcumin were lower than those for tetrahydrocurcumin, suggesting the highly pro-oxidative activity of curcumin. Curcumin has both oxidant and antioxidant properties. A causal link between the anti-inflammatory activities and molecular properties of phenolic antioxidants is suggested.
Murakami
Yukio
Y
Division of Oral Diagnosis, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado-City, Saitama 350-0283, Japan. ymura@dent.meikai.ac.jp
Ishii
Hiroaki
H
Takada
Naoki
N
Tanaka
Shoji
S
Machino
Mamoru
M
Ito
Shigeru
S
Fujisawa
Seiichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors; D006860:Hydrogen Bonding; D006878:Hydroxides / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D019800:Phenol / Q000737:chemistry; D016966:Porphyromonas gingivalis / Q000166:cytology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D000893:Anti-Inflammatory Agents; D003474:Curcumin; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D006878:Hydroxides; D008070:Lipopolysaccharides; D019800:Phenol; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C096277:tetrahydrocurcumin; C496540:PTGS2 protein, human