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.