title: Melittin attenuates liver injury in thioacetamide-treated mice through modulating inflammation and fibrogenesis.
abstract: Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Following injury, an acute inflammation response takes place resulting in moderate cell necrosis and extracellular matrix damage. Melittin, the major bioactive component in the venom of honey bee Apis mellifera, is a 26-residue amphipathic peptide with well-known cytolytic, antimicrobial and proinflammatory properties. However, the molecular mechanisms responsible for the anti-inflammatory activity of melittin have not been elucidated in liver fibrosis. We investigated whether melittin ameliorates liver inflammation and fibrosis in thioacetamide (TAA)-induced liver fibrosis. Two groups of mice were treated with TAA (200 mg/L, in drinking water), one of the groups of mice was co-treated with melittin (0.1 mg/kg) for 12 weeks while the other was not. Hepatic stellate cells (HSCs) were cultured with tumor necrosis factor α in the absence or presence of melittin. Melittin suppresses the expression of proinflammatory cytokines through the nuclear factor (NF)-κB signaling pathway. Moreover, melittin reduces the activity of HSCs in vitro, and decreases the expression of fibrotic gene responses in TAA-induced liver fibrosis. Taken together, melittin prevents TAA-induced liver fibrosis by inhibiting liver inflammation and fibrosis, the mechanism of which is the interruption of the NF-κB signaling pathway. These results suggest that melittin could be an effective agent for preventing liver fibrosis.
authors.affiliation: Department of Pathology, Catholic University of Daegu, College of Medicine, 3056–6 Daemyung 4-Dong, Nam-Gu, Daegu 705–718, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yoon-Seup
authors.initials: YS
authors.lastname: Kum
authors.forename: Tae-Im
authors.initials: TI
authors.lastname: Lee
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Kim
authors.forename: Woo-Ram
authors.initials: WR
authors.lastname: Lee
authors.forename: Bong-Il
authors.initials: BI
authors.lastname: Kim
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000737:chemistry; D055166:Hepatic Stellate Cells / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008555:Melitten / Q000302:isolation & purification / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013853:Thioacetamide; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001514:Bee Venoms; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013853:Thioacetamide; D008555:Melitten