Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells.
It has been reported that Rhusverniciflua exhibits anti-inflammatory, anti-oxidant and anti-cancer activities. However, little is known about biological activity of sulfuretin, a flavonoid isolated from R.verniciflua. In the present study, we investigated the anti-inflammatory effect and the underlying molecular mechanisms of sulfuretin in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Sulfuretin dose-dependently reduced the productions of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta) induced by LPS. Consistent with these findings, sulfuretin significantly suppressed the LPS-induced expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-alpha, and IL-1 beta. In addition, sulfuretin attenuated LPS-induced DNA binding and the transcriptional activities of nuclear factor-kappa B (NF-kappaB), which was accompanied by a parallel reduction of degradation and phosphorylation of inhibitory kappa B-alpha (I kappaB-alpha) and consequently by decreased nuclear translocation of p65 subunit of NF-kappaB. Furthermore, pretreatment with sulfuretin significantly inhibited the LPS-stimulated activation of I kappaB kinase beta (IKK beta). Taken together, these results suggest that the anti-inflammatory effect of sulfuretin in LPS-treated RAW 264.7 macrophages is associated with the suppression of NF-kappaB transcriptional activity via the inhibitory regulation of IKKbeta phosphorylation.
Shin
Ji-Sun
JS
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Park
Young Mi
YM
Choi
Jung-Hye
JH
Park
Hee-Juhn
HJ
Shin
Min Cheol
MC
Lee
Yong Sup
YS
Lee
Kyung-Tae
KT
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005419:Flavonoids / Q000494:pharmacology; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D029045:Rhus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C054989:sulfuretin