OBJECTIVE Highly electronegative L5 low-density lipoprotein(LDL),an atherogenic LDL,induces endothelial cell(EC)senescence and has been implicated in the progression of atherosclerosis.We examine whether sesamol,a nat...OBJECTIVE Highly electronegative L5 low-density lipoprotein(LDL),an atherogenic LDL,induces endothelial cell(EC)senescence and has been implicated in the progression of atherosclerosis.We examine whether sesamol,a natural organic compound and component of sesame oil,prevents EC senescence induced by electronegative LDL(L5)and to investigate the underlying mechanisms.METHODS Syrian hamsters,which have a LDL profile similar to that of humans,were fed a normal chow diet(control),a high-fat diet(HFD),or a HFD supplemented with the administration of 50 or 100mg·kg-1 sesamol via oral gavage(HFD+sesamol)for 16 weeks(n=10 per group).Among these groups,we compared plasma L5 levels and aortic endothelial senescence in the aortic arch.In vitro,we examined the effects of sesamol on human aortic endothelial cell(HAEC)senescence and signaling pathways induced by L5.RESULTS Hamsters in the HFD group had higher plasma L5 levels than did the HFD+sesamol groups or control group.Betagalactosidase(gal)staining showed that aortic endothelial senescence was markedly increased in the aortic arch of the HFD group but not in that of the HFD+sesamol groups when compared with the control group.In vitro,treatment of HAECs with sesamol(1-3mol·L-1)blocked L5-induced EC senescence in a dose-dependent manner.Sesamol also markedly inhibited the L5-induced phosphorylation of p38 MAPK and p53 activation and increased Mdm2 and phosphorylation of Akt.CONCLUSION The critical findings of this study suggest that sesamol may provide protection against atherosclerosis and the development of cardiovascular disease in humans.展开更多
本实验探究不同因素对高温条件下芝麻林素转化为芝麻酚的影响及其转化动力学,并通过液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)分析相关转化路径。结果表明:丙三醇是芝麻林素转化为芝麻酚的理想介质...本实验探究不同因素对高温条件下芝麻林素转化为芝麻酚的影响及其转化动力学,并通过液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)分析相关转化路径。结果表明:丙三醇是芝麻林素转化为芝麻酚的理想介质,反应温度和反应时间对芝麻酚生成率影响显著;在160~200℃范围内,芝麻林素的转化符合一级动力学方程特征,且反应速率常数与温度呈正相关,半衰期和十分之一衰期与温度呈负相关,通过阿伦尼乌斯方程计算出该反应活化能为(104.50±4.32)kJ/mol;LC-MS/MS分析结果表明以芝麻林素为底物的反应系统包括芝麻酚的生成和转化两条转化路径。展开更多
基金The project supported by the National Science Council of Cinese Taipei(NSC102-2320-B-039-058)China Medical University,Chinese Taipei(CMU102-N-02and CMU103-N-08)
文摘OBJECTIVE Highly electronegative L5 low-density lipoprotein(LDL),an atherogenic LDL,induces endothelial cell(EC)senescence and has been implicated in the progression of atherosclerosis.We examine whether sesamol,a natural organic compound and component of sesame oil,prevents EC senescence induced by electronegative LDL(L5)and to investigate the underlying mechanisms.METHODS Syrian hamsters,which have a LDL profile similar to that of humans,were fed a normal chow diet(control),a high-fat diet(HFD),or a HFD supplemented with the administration of 50 or 100mg·kg-1 sesamol via oral gavage(HFD+sesamol)for 16 weeks(n=10 per group).Among these groups,we compared plasma L5 levels and aortic endothelial senescence in the aortic arch.In vitro,we examined the effects of sesamol on human aortic endothelial cell(HAEC)senescence and signaling pathways induced by L5.RESULTS Hamsters in the HFD group had higher plasma L5 levels than did the HFD+sesamol groups or control group.Betagalactosidase(gal)staining showed that aortic endothelial senescence was markedly increased in the aortic arch of the HFD group but not in that of the HFD+sesamol groups when compared with the control group.In vitro,treatment of HAECs with sesamol(1-3mol·L-1)blocked L5-induced EC senescence in a dose-dependent manner.Sesamol also markedly inhibited the L5-induced phosphorylation of p38 MAPK and p53 activation and increased Mdm2 and phosphorylation of Akt.CONCLUSION The critical findings of this study suggest that sesamol may provide protection against atherosclerosis and the development of cardiovascular disease in humans.
文摘本实验探究不同因素对高温条件下芝麻林素转化为芝麻酚的影响及其转化动力学,并通过液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry,LC-MS/MS)分析相关转化路径。结果表明:丙三醇是芝麻林素转化为芝麻酚的理想介质,反应温度和反应时间对芝麻酚生成率影响显著;在160~200℃范围内,芝麻林素的转化符合一级动力学方程特征,且反应速率常数与温度呈正相关,半衰期和十分之一衰期与温度呈负相关,通过阿伦尼乌斯方程计算出该反应活化能为(104.50±4.32)kJ/mol;LC-MS/MS分析结果表明以芝麻林素为底物的反应系统包括芝麻酚的生成和转化两条转化路径。