Paeonol is a phenolic compound isolated mainly from Moutan cortex, root bark of Chinese Peony tree. Moutan cortex holds a significant value in traditional Chinese medicine for alleviating various oxidative stress-related diseases mainly atherosclerosis and myocardial infarction. The present study seeks to identify the protective mechanisms of paeonol in oxidative stress-induced premature senescence in endothelial cells.

HUVECs were pretreated with paeonol or DMSO control at different doses for 24 h prior to an exposure of 200 μM of reactive oxygen species (ROS) inducer, hydrogen peroxide (H₂O₂). The protective effects of paeonol against H₂O₂-induced senescence were evaluated and the activation of Sirtuin 1 pathway by paeonol pretreatment was investigated in HUVECs.

Paeonol attenuated H₂O₂-induced cell growth arrest at G0/G1 phase, reduced the percentage of SA-β-Gal positive cells and increased BrdU incorporation. In addition, enzymatic Sirt1 activation assay indicated that paeonol significantly increased lysyl deactylase activity of Sirt1 enzyme with a fold change of 2.4±0.195 (p<0.05). Furthermore, pretreatment with paeonol significantly decreased the levels of p53, acetyl H3K14 and H4K16 protein expression upregulated by H₂O₂ stimulation. The changes in the histone protein levels were accompanied with an increase in Sirt1 protein expression level.

These findings suggest that paeonol protects endothelial cells against oxidative stress-induced premature senescence by modulating the expressions of Sirt1 protein and its substrates.