Based on the previous research that
oroxylin A can suppress
inflammation, we investigated the hepatoprotective role of
oroxylin A against CCl₄-induced liver damage in mice and then studied the possible alteration of the activities of
cytokine signaling participating in liver regeneration. Wild type (WT) mice were orally administrated with
oroxylin A (60 mg/kg) for 4 days after CCl₄ injection, the anti-inflammatory effects of
oroxylin A were assessed directly by hepatic histology and indirectly by measuring serum levels of
aspartate aminotransferase (AST),
alanine aminotransferase (ALT) and
Albumin.
Proliferating cell nuclear antigen (
PCNA) staining was performed to evaluate the role of
oroxylin A in promoting hepatocyte proliferation. Serum IL-1β, TNF-α,
IL-6 and
IL-1Ra levels were measured by
enzyme-linked
immunosorbent assay (ELISA) and liver HGF,
EGF, TNF-α,
IL-6,
IL-1Ra and IL-1β gene expression was determined by quantitative real-time PCR. The data indicated that the
IL-6 and TNF-α
mRNA of
oroxylin A administered group significantly increased higher than the control within 12 hours after CCl4 treatment. Meanwhile,
oroxylin A significantly enhanced the expression of
IL-1Ra at the early phase, which indicated that
oroxylin A could facilitate the initiating events in liver regeneration by increasing
IL-1Ra which acts as an
Acute-Phase Protein (APP). In addition, a lethal CCl₄-induced
acute liver failure model offers a survival benefit in
oroxylin A treated WT mice. However,
oroxylin A could not significantly improve the percent survival of IL-1RI⁻/⁻ mice with a lethal CCl₄-induced
acute liver failure.
CONCLUSIONS: Our study confirmed that
oroxylin A could strongly promote liver structural remodeling and functional recovery through IL-1Ra/IL-1RI signaling pathway. All these results support the possibility of
oroxylin A being a therapeutic candidate for acute liver injury.