title: Anti-inflammatory effects and molecular mechanisms of 8-prenyl quercetin.
abstract: 8-prenyl quercetin (PQ) is a typical prenylflavonoid distributed in plant foods. It shows higher potential bioactivity than its parent quercetin (Q) although the mechanisms are not fully understood. This study aims to clarify the anti-inflammatory effects and molecular mechanisms of PQ in cell and animal models, compared to Q.
  
  
  
  RAW264.7 cells were treated with PQ or Q to investigate the influence on the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and protein kinases by Western blotting. Nitric oxide (NO) and prostaglandin E2 (PGE2 ) were measured by the Griess method and ELISA, respectively. Cytokines were assayed by the multiplex technology. Mouse paw edema was induced by LPS. The results revealed that PQ had stronger inhibition on the production of iNOS, COX-2, NO, PGE2 , and 12 kinds of cytokines, than Q. PQ also showed in vivo anti-inflammatory effect by attenuating mouse paw edema. Molecular data revealed that PQ had no competitive binding to Toll-like receptor 4 with LPS, but directly targeted SEK1-JNK1/2 (where SEK is stress-activated protein kinase and JNK1/2 is Jun-N-terminal kinase 1/2) and MEK1-ERK1/2 (where ERK is extracellular signal regulated kinase).
  
  
  
  PQ as a potential inhibitor revealed anti-inflammatory effect in both cell and animal models at least by targeting SEK1-JNK1/2 and MEK1-ERK1/2.
authors.affiliation: The United Graduate School of Agricultural Science, Kagoshima University, Kagoshima, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Hisanaga
authors.affiliation: Department of Food Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Mukai
authors.affiliation: The United Graduate School of Agricultural Science, Kagoshima University, Kagoshima, Japan.|Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Sakao
authors.affiliation: Department of Food Science, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Terao
authors.affiliation: The United Graduate School of Agricultural Science, Kagoshima University, Kagoshima, Japan.|Faculty of Agriculture, Kagoshima University, Kagoshima, Japan.
authors.forename: De-Xing
authors.initials: DX
authors.lastname: Hou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000209:etiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011487:Protein Conformation; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C000625221:8-prenyl quercetin; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone
keywords: Cellular signaling; Direct binding; Inflammatory mediators; Molecular targets; Prenyl quercetin