Inhibitory effect of the alkyl side chain of caffeic acid analogues on lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages.
Caffeic acid esters, one of the components of propolis, are known to show a variety of biological effects such as anti-tumor, anti-oxidant, and anti-inflammatory activities. Although, the anti-inflammatory activities of caffeic acid esters have been studied by analyzing their structure, the detailed mechanisms of their activities remain unclear. Thus, in this study, we examined the function of the ester functional group and the alkyl side chain (alcoholic part) and transformed caffeic acid to several derivatives. The inhibitory effect of these derivatives on NO production in murine macrophage RAW264.7 cells was dependent on the length and size of the alkyl moiety, and undecyl caffeate was the most potent inhibitor of NO production. In addition, individual experiments using undecanol, caffeic acid, undecanol plus caffeic acid, and undecyl caffeate showed that the connection between caffeic acid and the alkyl chain is critical for activity. Amide and ketone derivatives showed that not only the ester functional group but also the amide and ketone functional groups exhibit an inhibitory effect on NO production.
Uwai
Koji
K
Laboratory of Pharmaceutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Osanai
Yuu
Y
Imaizumi
Takuma
T
Kanno
Syu-ichi
S
Takeshita
Mitsuhiro
M
Ishikawa
Masaaki
M
D000818:Animals; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005562:Formazans / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000032:analysis; D011429:Propolis / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts / Q000737:chemistry
D002109:Caffeic Acids; D005562:Formazans; D008070:Lipopolysaccharides; D009573:Nitrites; D013778:Tetrazolium Salts; C581629:caffeic acid undecyl ester; C079782:MTT formazan; D009569:Nitric Oxide; D011429:Propolis