title: β-Caryophyllene alleviates D-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the TLR4 and RAGE signaling pathways.
abstract: 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 200 mg/kg) 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) injection and were killed 1 h or 6 h 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.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Hong-Ik
authors.initials: HI
authors.lastname: Cho
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jeong-Min
authors.initials: JM
authors.lastname: Hong
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Joo-Wan
authors.initials: JW
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Hyo-Sun
authors.initials: HS
authors.lastname: Choi
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Hwan Kwak
authors.affiliation: Division of Bioscience, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Dong-Ung
authors.initials: DU
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Sang
authors.initials: S
authors.lastname: Kook Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon, Gyeonggi-do 440-746, Republic of Korea. Electronic address: sunmee@skku.edu.
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D005688:Galactosamine; D018836:Inflammation Mediators / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D000067759:Receptor for Advanced Glycation End Products / Q000187:drug effects* / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism
chemical_list: C000593873:Ager protein, mouse; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D000081223:Polycyclic Sesquiterpenes; D000067759:Receptor for Advanced Glycation End Products; D012717:Sesquiterpenes; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D005688:Galactosamine; C024714:caryophyllene; D020928:Mitogen-Activated Protein Kinases
keywords: Fulminant hepatic failure; High-mobility group box 1; Receptor for advanced glycation end products; Toll-like receptor 4; β-Caryophyllene