Conclusion
Therefore, these aggregated data suggested that oroxylin A relieved alcoholic liver injury possibly by inhibiting the senescence of hepatocyte, which was dependent on its activation of YAP in hepatocytes.
Methods
Male ICR mice and human hepatocyte cell line LO2 were used. Yes-associated protein (YAP) overexpression and knockdown were achieved using plasmid and siRNA technique. Cellular senescence was assessed by analyses of the senescence-associated β-galactosidase (SA-β-gal), senescence marker p16, p21, Hmga1, cell cycle and telomerase activity.
Results
Oroxylin A alleviated ethanol-induced hepatocyte damage by suppressing activities of supernatant marker enzymes. We found that oroxylin A inhibited ethanol-induced hepatocyte senescence by decreasing the number of SA-β-gal-positive LO2 cells and reducing the expression of senescence markers p16, p21 and Hmga1 in vitro. Moreover, oroxylin A affected the cell cycle and telomerase activity. Of importance, we revealed that YAP pharmacological inhibitor verteporfin or YAP siRNA eliminated the effect of oroxylin A on ethanol-induced hepatocyte senescence in vitro, and this was further supported by the evidence in vivo experiments.