Protective Mechanism of Anethole on Hepatic Ischemia/Reperfusion Injury in Mice

• Published in: Journal of natural products (Washington, D.C.) Vol. 76; no. 9; pp. 1717 - 1723
• Main Authors: Cho, Hong-Ik, Kim, Kang-Min, Kwak, Jong Hwan, Lee, Sang Kook, Lee, Sun-Mee
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 27.09.2013
• Subjects: Animals; Anisoles - chemistry; Anisoles - pharmacology; Blotting, Western; Fruit - chemistry; HMGB Proteins - metabolism; HMGB1 Protein - metabolism; Interferon Regulatory Factor-1 - genetics; Interleukin-6 - analysis; Interleukin-6 - blood; Ischemia - pathology; JNK Mitogen-Activated Protein Kinases - drug effects; JNK Mitogen-Activated Protein Kinases - metabolism; Liver - pathology; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred Strains; Molecular Structure; NF-kappa B - drug effects; Reperfusion Injury - blood; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Republic of Korea; Toll-Like Receptor 4 - drug effects; Toll-Like Receptor 4 - metabolism; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - blood; Republic of Korea
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np4004323

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.