Rosmarinic acid protects mice from Concanavalin A-induced hepatic injury through AMPK signaling

Rosmarinic acid (RA) is extensively utilized in herbal medicine in China. The adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling can be activated by RA and inhibited by the synthetic, reversible AMP-competitive inhibitor, Compound C (CC). The objective of this study was to investigate the role of AMPK signaling involving the protective effects of RA on concanavalin A (Con A)-induced(AIH) in mice. BALB/c mice were treated with RA, with or without CC, followed by the pretreatment with concanavalin A(Con A). Analysis of serum aminotransferases and cytokines were conducted and liver tissue histology was performed to evaluate hepatic injury. Cytokine levels in serum and hepatic tissue were respectively measured by enzyme-linked immunoassay (ELISA) and used quantitative polymerase chain reaction (qPCR). Levels of phosphorylated acetyl coenzyme-A carboxylase in the liver, representing AMPK activation，were detected by Western blotting. Compared with the Con A group, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in RA group (100 and 150 mg/kg/day) were significantly reduced. RA also reduced hepatocyte swelling, cell death, and infiltration of leukocytes in the liver of Con A-treated mice. Serum levels of cytokines, such as interferon-γ(IFN-γ), interleukin-2 (IL-2) and interferon-1(IL-1β), were reduced by RA pretreatment, while the levels of serum interferon-10 (IL-10), an anti-inflammatory cytokine, was elevated. These protective effects were reversed by treatment with CC. RA treatment reduced the hepatic damage via the activation of AMPK in the mice of Con A-induced. So RA acts as a potential part in the therapy of autoimmune hepatitis.

Keywords: Concanavalin A; Rosmarnic acid; adenosine 5'-monophosphate protein kinase; autoimmune hepatitis.