RRC ID 42420
Author Hirata A, Murakami Y, Atsumi T, Shoji M, Ogiwara T, Shibuya K, Ito S, Yokoe I, Fujisawa S.
Title Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages.
Journal In Vivo
Abstract Phenylpropanoids may act as nonsteroidal anti-inflammatory drug (NSAID)-like compounds. 4-cis, 8-cis-Bis (4-hydroxy-3-methoxyphenyl)-3, 7-dioxabicyclo-[3.3.0]octane-2,6-dione (bis-FA, compound 2), a dimer of ferulic acid, was synthesized from ferulic acid (1), and its effect on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) expression in RAW 264.7 cells was compared with those of the parent ferulic acid (1) and of iso-ferulic acid (3-hydroxy-4-methoxycinnamic acid) (3). LPS-induced gene expression of COX-2 was markedly inhibited by compound 2 at a concentration of 10 microM and by compound 3 at 100 microM, but was not inhibited by compound 1 at 100 microM. This observation suggests that compound 2 may possess potent anti-inflammatory activity. These ferulic acid-related compounds were able to scavenge the stable 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. The 50% inhibitory concentration for DPPH radicals declined in the order 3 (40.20 mM) > 2 (3.16 mM) > 1 (0.145 mM). Compound 1 possessed potent anti-radical activity, but no COX-2 inhibitory activity, which may be a result of enhancement of its conjugate properties by abstraction of an H atom from the phenolic OH group, causing loss of phenolic function. In contrast, inhibition of COX-2 expression by compounds 2 and 3 could be caused by their increased phenolic function, which is associated with decreased anti-radical activity. Compounds 2 and 3, particularly 2, may have potential as NSAID-like compounds.
Volume 19(5)
Pages 849-53
Published 2005-1-1
PMID 16097437
MeSH Actins / chemistry Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology Antioxidants / chemistry Biphenyl Compounds / pharmacology Blotting, Northern Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis Bridged Bicyclo Compounds, Heterocyclic / pharmacology* Cell Line Cinnamates / pharmacology Coumaric Acids / chemistry* Coumaric Acids / pharmacology* Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Cyclooxygenase Inhibitors / pharmacology DNA / chemistry Dimerization Dose-Response Relationship, Drug Free Radical Scavengers / pharmacology Free Radicals Guaiacol / analogs & derivatives* Guaiacol / chemical synthesis Guaiacol / pharmacology Hydrazines / pharmacology Inhibitory Concentration 50 Lipopolysaccharides / pharmacology* Macrophages / drug effects Macrophages / enzymology* Mice Models, Chemical Nucleic Acid Hybridization Phenol / chemistry Picrates Prostaglandin-Endoperoxide Synthases / biosynthesis*
IF 1.541
Times Cited 28
Human and Animal Cells RAW 264(RCB0535)