β-Caryophyllene alleviates d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways

• Published in: European journal of pharmacology 2015-10, Vol.764, p.613-621
• Main Authors: Cho, Hong-Ik, Hong, Jeong-Min, Choi, Joo-Wan, Choi, Hyo-Sun, Hwan Kwak, Jong, Lee, Dong-Ung, Kook Lee, Sang, Lee, Sun-Mee
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cells, Cultured; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Cytokines - metabolism; Cytoprotection; Disease Models, Animal; Fulminant hepatic failure; Galactosamine; High-mobility group box 1; Inflammation Mediators - metabolism; Kupffer Cells - drug effects; Kupffer Cells - metabolism; Kupffer Cells - pathology; Lipopolysaccharides; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Failure - metabolism; Liver Failure - pathology; Liver Failure - prevention & control; Male; Mice, Inbred ICR; Mitogen-Activated Protein Kinases - metabolism; Receptor for advanced glycation end products; Receptor for Advanced Glycation End Products - drug effects; Receptor for Advanced Glycation End Products - metabolism; Sesquiterpenes - pharmacology; Signal Transduction - drug effects; Time Factors; Toll-like receptor 4; Toll-Like Receptor 4 - drug effects; Toll-Like Receptor 4 - metabolism; β-Caryophyllene
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2015.08.001

Agastache rugosa (A. rugosa, Labiatae), a perennial herb spread throughout Korean fields, is widely consumed as a wild edible vegetable and is used in folk medicine. This study examined the hepatoprotective mechanisms of β-caryophyllene (BCP), a major bicyclic sesquiterpene of A. rugosa, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. Mice were given an intraperitoneal injection of BCP (50, 100 and 200mg/kg) 1h before GalN (800mg/kg)/LPS (40μg/kg) injection and were killed 1h or 6h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, both of which were attenuated by BCP. BCP also attenuated increases in serum tumor necrosis factor-α, interleukin 6, and high-mobility group protein B1 levels by GalN/LPS. GalN/LPS significantly increased toll-like receptor (TLR) 4 and receptor for advanced glycation end products (RAGE) protein expression, extracellular signal-related kinase, p38 and c-Jun N-terminal kinase phosphorylation, nuclear factor κB (NF-κB), early growth response protein-1, and macrophage inflammatory protein-2 protein expression. These increases were attenuated by BCP. Furthermore, BCP suppressed increased TLR4 and RAGE protein expression and proinflammatory cytokines production in LPS-treated isolated Kupffer cells. Our findings suggest that BCP protects against GalN/LPS-induced liver injury through down-regulation of the TLR4 and RAGE signaling. [Display omitted]