Anti-inflammatory effects of sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor-kappaB inactivation.
To investigate the anti-inflammatory potential of sinapic acid as well as the underlying mechanism involved, we studied the inhibitory effect of sinapic acid on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effect. Sinapic acid inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E 2 (PGE 2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta production in a dose-dependent manner. Consistent with these findings, sinapic acid inhibited LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-alpha, and IL-1beta mRNA expression in RAW 264.7 macrophages, as determined by Western blotting and reverse-transcribed polymerase chain reaction, respectively. Sinapic acid suppressed the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), a transcription factor pivotal necessary for pro-inflammatory mediators, such as iNOS, COX-2, TNF-alpha, and IL-1beta. This effect was accompanied by a parallel reduction of the nuclear translocation of p65 and p50 NF-kappaB subunits, as well as IkappaB-alpha degradation and phosphorylation. The effects of sinapic acid on acute phase inflammation were investigated on serotonin- and carrageenan-induced paw edema and compared with indomethacin (10 mg/kg, p.o.) or ibuprofen (100 mg/kg, p.o.). Maximum inhibitions of 34.2 and 44.5% were observed at a concentration of 30 mg/kg for serotonin- and carrageenan-induced paw edema, respectively. These results suggest that the suppressions of the expressions of iNOS, COX-2, TNF-alpha, and IL-1beta via NF-kappaB inactivation are responsible for the anti-inflammatory effects of sinapic acid.
College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Seoul 130-701, Republic of Korea.
Kyung-Jin
KJ
Yun
Duck-Jae
DJ
Koh
Shi-Hye
SH
Kim
Seung Jae
SJ
Park
Jong Hoon
JH
Ryu
Deog-Gon
DG
Kim
Jin-Yong
JY
Lee
Kyung-Tae
KT
Lee
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003373:Coumaric Acids / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D003373:Coumaric Acids; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; C073734:sinapinic acid; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2