title: Dietary supplementation with geranylgeraniol suppresses lipopolysaccharide-induced inflammation via inhibition of nuclear factor-κB activation in rats.
abstract: OBJECTIVE
  The isoprenoid geranylgeraniol (GGOH) inhibits nuclear factor-kappa B (NF-κB) activation in the liver, yet the mechanism remains unclear. We investigated the modulation and inhibition of lipopolysaccharide (LPS)-induced NF-κB signaling in the liver of rats fed a GGOH-supplemented diet.
  
  
  METHODS
  Rats were fed a diet supplemented with or without GGOH for 10 days. Rats were then intraperitoneally injected with 0.5 mg/kg LPS or vehicle (sterilized saline) and fasted for 18 h. Plasma levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the liver damage indicators alanine and aspartate aminotransferases (ALT and AST) were assessed. Liver mRNA and proteins were assayed for changes in NF-κB target genes and signal transduction genes.
  
  
  RESULTS
  Rats fed a high-dose, GGOH-supplemented diet showed significantly lower levels of plasma inflammatory cytokines and ALT and AST activities. In the liver, GGOH significantly suppressed NF-κB activation and mRNA expression of its pro-inflammatory target genes. Furthermore, GGOH supplementation substantially suppressed mRNA expression of signal transducer genes upstream of the IκB kinase complex. Western blotting of liver extracts further demonstrated the substantial decrease in total IL-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6), leading to lower signal transduction and inhibition of NF-κB after LPS.
  
  
  CONCLUSIONS
  A 10-day, high-dose, GGOH-supplemented diet was sufficient to inhibit LPS-induced inflammation and activation of NF-κB in rat livers. GGOH significantly modulated NF-κB signaling molecules, inhibiting its signal transduction and activation in the liver, thus protecting against liver damage.
authors: Laboratory of Nutrition, Graduate School of Agricultural Sciences, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Sendai, Japan.
authors: Puspo E
authors: PE
authors: Giriwono
authors: Hitoshi
authors: H
authors: Shirakawa
authors: Yusuke
authors: Y
authors: Ohsaki
authors: Shuichi
authors: S
authors: Hata
authors: Hiroki
authors: H
authors: Kuriyama
authors: Shoko
authors: S
authors: Sato
authors: Tomoko
authors: T
authors: Goto
authors: Michio
authors: M
authors: Komai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements; D004224:Diterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D015536:Down-Regulation; D048550:Hepatic Insufficiency / Q000209:etiology / Q000517:prevention & control; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048029:TNF Receptor-Associated Factor 6; C017338:geranylgeraniol; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases; D051550:I-kappa B Kinase