摘要
Objective:To investigate the effect of honokiol on oxidative damage in HaCaT human keratinocytes.Methods:HaCaT cells were exposed to hydrogen peroxide(H_(2)O_(2)),following pretreatment with various concentrations of honokiol.The alleviating effects of honokiol on HaCaT cell viability and cell death,reactive oxygen species(ROS)production,DNA damage,mitochondrial dynamics,and inhibition of adenosine triphoaphate production against H_(2)O_(2)were investigated.Western blotting analysis was used to analyze the expression levels of specific proteins.Results:Honokiol suppressed H_(2)O_(2)-induced cytotoxicity and DNA damage by blocking abnormal ROS accumulation.Honokiol also prevented apoptosis by inhibiting loss of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol,decreasing the Bax/Bcl-2 ratio,and reducing the activity of caspase-3 in H_(2)O_(2)-stimulated HaCaT cells.In addition,honokiol attenuated H_(2)O_(2)-induced reduction of adenosine triphosphate content,and activation of AMP-activated protein kinase(AMPK)was markedly promoted by honokiol in H_(2)O_(2)-stimulated cells.Importantly,the anti-apoptosis and anti-proliferative activity of honokiol against H_(2)O_(2)was further enhanced by adding an activator of AMPK,indicating that honokiol activated AMPK in HaCaT keratinocytes to protect against oxidative damage.Conclusions:The present results indicate that honokiol may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases.