Jamal Juliana, Mustafa Mohd Rais, Wong Pooi-Fong
Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia.
Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia.
J Ethnopharmacol. 2014 Jun 11;154(2):428-36. doi: 10.1016/j.jep.2014.04.025. Epub 2014 Apr 24.
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 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.
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.
丹皮酚是一种主要从牡丹皮（牡丹树的根皮）中分离出的酚类化合物。牡丹皮在传统中药中对于缓解各种氧化应激相关疾病（主要是动脉粥样硬化和心肌梗死）具有重要价值。本研究旨在确定丹皮酚在氧化应激诱导的内皮细胞早衰中的保护机制。
在暴露于200μM活性氧（ROS）诱导剂过氧化氢（H2O2）之前，用不同剂量的丹皮酚或二甲基亚砜（DMSO）对照预处理人脐静脉内皮细胞（HUVECs）24小时。评估丹皮酚对H2O2诱导的衰老的保护作用，并研究丹皮酚预处理对HUVECs中沉默调节蛋白1（Sirtuin 1）途径的激活情况。
丹皮酚减轻了H2O2诱导的细胞在G0/G1期的生长停滞，降低了衰老相关β-半乳糖苷酶（SA-β-Gal）阳性细胞的百分比，并增加了5-溴脱氧尿嘧啶核苷（BrdU）掺入。此外，酶促Sirt1激活试验表明，丹皮酚显著增加了Sirt1酶的赖氨酰脱酰酶活性，倍数变化为2.4±0.195（p<0.05）。此外，丹皮酚预处理显著降低了H2O2刺激上调的p53、乙酰化组蛋白H3K14和H4K16蛋白表达水平。组蛋白水平的变化伴随着Sirt1蛋白表达水平的增加。
这些发现表明，丹皮酚通过调节Sirt1蛋白及其底物的表达来保护内皮细胞免受氧化应激诱导的早衰。
