title: O-Methylated flavonol isorhamnetin prevents acute inflammation through blocking of NF-κB activation.
abstract: Here, we isolated isorhamnetin, a natural 3'-O-methylated flavonoid, from water dropwort (Oenanthe javanica, Umbelliferae) and investigated its ability to protect against acute inflammation in vivo and in vitro. To induce paw swelling, the hind paw of each rat was injected with a carrageenan 1h after vehicle or isorhamnetin treatment. In vitro effect and mechanism studies were performed in lipopolysaccharide (LPS)-activated macrophages. Administration of isorhamnetin markedly inhibited the swelling volume and the thickness of hind paws. Moreover, isorhamnetin significantly reduced inflammatory cell infiltration and pro-inflammatory gene expression in rats. Isorhamnetin pretreatment inhibited inducible nitric oxide synthase (iNOS) expression and NO release in LPS-stimulated cells. Activation of nuclear factor-kappa B (NF-κB) and activating protein-1 (AP-1) is the key step in the iNOS gene induction. Isorhamnetin specifically inhibited NF-κB luciferase activity, but not AP-1. Pretreatment with isorhamnetin suppressed NF-κB nuclear translocation in accordance with decreased phosphorylation and degradation of inhibitory-κB. Consistently, TNF-α, IL-1β and IL-6 expression, representative NF-κB target genes, were almost completely prohibited by isorhamnetin. Furthermore, isorhamnetin inhibited LPS-induced JNK and AKT/IKKα/β phosphorylation. Our results suggest that isorhamnetin inhibited JNK, and AKT/IKKα/β activation, leading to NF-κB inactivation, which might contribute to the inhibition of the acute inflammatory response.
authors.affiliation: College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Yang
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Shin
authors.forename: So Hee
authors.initials: SH
authors.lastname: Jin
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Jo
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Jegal
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Lee
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Cho
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Ki
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004487:Edema / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020834:Ethnopharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008518:Medicine, East Asian Traditional; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D031050:Oenanthe / Q000737:chemistry; D021381:Protein Transport / Q000187:drug effects; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D056910:Republic of Korea; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; C047368:3-methylquercetin; D011794:Quercetin
keywords: AP-1; Anti-inflammation; H&E; Hematoxylin & Eosin; IKK; IL; Isorhamnetin; IκB; IκB kinase; JNK; LPS; MAPK; MPO; NF-κB; NO; NOS; Nuclear factor-kappa B (NF-κB); PI3K; TLR; TNF; activating protein-1; inhibitory κB; interleukin; lipopolysaccharide; mitogen-activated protein kinase; myeloperoxidase; nitric oxide; nitric oxide synthase; nuclear factor-kappa B; phosphatidylinositol 3-kinase; toll-like receptor; tumor necrosis factor