Inhibitory effect of 2'-hydroxycinnamaldehyde on nitric oxide production through inhibition of NF-kappa B activation in RAW 264.7 cells.
Cinnamomum cassia has been widely used for treating dyspepsia, gastritis, and inflammatory disease. In the present study, several of cinnamaldehyde derivatives were synthesized from various cinnamic acid based on the 2'-hydroxycinnamaldehyde isolated from the bark C. cassia Blume was investigated to compare their NO production and NF-kappa B activity from Raw 264.7 cell since nitric oxide (NO) and NF-kappa B have been shown to be implicated factors in the inflammatory disease. The results show that HCA, among the derivatives, most significantly inhibited lipopolysaccharide (LPS)-induced NO production and NF-kappa B transcriptional activity in a dose-dependent manner with an IC(50) value of 8 and 22 microM, respectively. We next investigated putative possible mechanisms of inhibitory effect of HCA on NO production. The inhibition of NO by HCA was consistent with the inhibitory effect on LPS-induced inducible nitric oxide synthase (iNOS) expression. Moreover, HCA inhibited LPS-induced p50 and p65 translocation resulting in the inhibition of the DNA binding activity of the NF-kappa B, a central regulator of iNOS. The present results provided evidence that HCA, among cinnamaledhyde derivatives, has the most inhibitory effect on NO production through inhibition of NF-kappa B activation, and thus can be used as an anti-inflammatory agent.
Lee
Seung Ho
SH
College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju 361-763, South Korea.
Lee
Sun Young
SY
Son
Dong Ju
DJ
Lee
Heesoon
H
Yoo
Hwan Soo
HS
Song
Sukgil
S
Oh
Ki Wan
KW
Han
Dong Cho
DC
Kwon
Byoung Mog
BM
Hong
Jin Tae
JT
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D032904:Cinnamomum aromaticum / Q000737:chemistry*; D051546:Cyclooxygenase 2; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology
D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D000171:Acrolein; D004247:DNA; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse; C012843:cinnamaldehyde