title: Protective mechanism of anethole on hepatic ischemia/reperfusion injury in mice.
abstract: The aim of this study was to investigate the hepatoprotective effect of anethole (trans-anethole, 1), a major component of Foeniculum vulgare, and its molecular mechanism during ischemia/reperfusion (I/R). Mice were subjected to 60 min of partial hepatic ischemia followed by 1 and 6 h of reperfusion. Compound 1 (50, 100, and 200 mg/kg) or the vehicle alone (10% Tween 80-saline) was orally administered 1 h prior to ischemia. After 1 and 6 h of reperfusion, serum alanine aminotransferase, tumor necrosis factor-α, and interleukin 6 levels significantly increased, but these increases were attenuated by 1. Nuclear translocation of interferon regulatory factor (IRF)-1, release of high mobility group box (HMGB) 1 into the extracellular milieu, and the interactions between IRF-1 and histone acetyltransferase p300 increased after I/R. These increases were attenuated by 1. Compound 1 suppressed increases in toll-like receptor (TLR) 4, myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal-regulated kinase, c-Jun N-terminal kinase, nuclear translocation of nuclear factor kappa B, and phosphorylated c-Jun. The present findings suggest that 1 protects against hepatic I/R injury by suppression of IRF-1-mediated HMGB1 release and subsequent TLR activation.
authors: School of Pharmacy, Sungkyunkwan University , Suwon, Gyeonggi-do, 440-746, Republic of Korea.
authors: Hong-Ik
authors: HI
authors: Cho
authors: Kang-Min
authors: KM
authors: Kim
authors: Jong Hwan
authors: JH
authors: Kwak
authors: Sang Kook
authors: SK
authors: Lee
authors: Sun-Mee
authors: SM
authors: Lee
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D005638:Fruit / Q000737:chemistry; D024002:HMGB Proteins / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D050856:Interferon Regulatory Factor-1 / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D007511:Ischemia / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects; D015427:Reperfusion Injury / Q000097:blood* / Q000276:immunology / Q000473:pathology*; D056910:Republic of Korea; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000097:blood
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D024002:HMGB Proteins; D024243:HMGB1 Protein; D050856:Interferon Regulatory Factor-1; D015850:Interleukin-6; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; C006578:anethole