Juliana Jamal1, Mohd Rais Mustafa1, Pooi-Fong Wong2. 1. Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. 2. Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: wongpf@um.edu.my.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: HUVECs were pretreated with paeonol or DMSO control at different doses for 24h prior to an exposure of 200μM 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. RESULTS: 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. CONCLUSION: These findings suggest that paeonol protects endothelial cells against oxidative stress-induced premature senescence by modulating the expressions of Sirt1 protein and its substrates.
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: HUVECs were pretreated with paeonol or DMSO control at different doses for 24h prior to an exposure of 200μM 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. RESULTS: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. CONCLUSION: These findings suggest that paeonol protects endothelial cells against oxidative stress-induced premature senescence by modulating the expressions of Sirt1 protein and its substrates.
Authors: Juan Gui; Arne Potthast; Anne Rohrbach; Katja Borns; Anibh M Das; Frauke von Versen-Höynck Journal: Pediatr Res Date: 2015-12-30 Impact factor: 3.756