Abstract
IntroductionBased 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.ConclusionsOur 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.
Highlights
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 studied the possible alteration of the activities of cytokine signaling participating in liver regeneration
After CCl4 treatment, serum ALT and AST rapidly elevated to peak level at day 1, decreased thereafter, while oroxylin A treatment significantly inhibited the elevation of serum ALT and AST from day 1 to day 5 (Fig. 2A and B)
We found that serum Albumin significantly increased after oroxylin A administration compared to the control (Fig. 2C)
Summary
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 studied the possible alteration of the activities of cytokine signaling participating in liver regeneration. Oroxylin A (5, 7-Dihydroxy-6-methoxyflavone, C16H12O5, Fig. 1A) is a flavonoid isolated from Scutellaria baicalensis, which is one of the most important medicinal herbs in traditional Korean/Chinese/Japanese medicine It has been used as a promising candidate for analgesic, anti-pyretic, anti-inflammation, anti-cancer, antiviral and anti-bacterial infections [8]. Previous studies indicated that oroxylin A could selectively induce apoptosis of cancer cells and inhibit normal hepatocyte apoptosis, which arouse our interesting to study whether oroxylin A could facilitate liver regeneration after injury
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