Oxidative stress is one of the main causes of neurodegenerative diseases such as Alzheimer disease(AD).Our previous studies have shown that artemisinin,a anti-malaria Chinese medicine,with neuroprotective effect,howev...Oxidative stress is one of the main causes of neurodegenerative diseases such as Alzheimer disease(AD).Our previous studies have shown that artemisinin,a anti-malaria Chinese medicine,with neuroprotective effect,however,the antioxidative effect of artemisinin and its potential mechanism remain to be elucidated.In the present study,the protective effect and the underlying mechanism of artemisinin against injury of hydrogen peroxide(H_2O_2) in SH-SY5Y and hippocampal neurons were studied.Our results show that artemisinin protected SH-SY5Y and hippocampal neuronal cells from H_2O_2-induced cell death at clinically relevant concentrations in a concentration-dependent manner.Further studies showed that artemisinin significantly reduced cell death caused by H_2O_2 by restoring nuclear morphology,abnormal changes in intracellular ROS,activation of caspase 3,lactate dehydrogenase release and mitochondrial membrane potential.Hoechst staining and flow cytometry showed that artemisinin significantly reduced the apoptosis of SH-SY5Y cells exposed to H_2O_2.Western blotting analysis showed that artemisinin stimulated the phosphorylation and activation of AMP-activated protein kinase(AMPK) in SH-SY5Y cells in a time and concentration-dependent manner,whereas the application of AMPK inhibitor Compound C or decrease in expression of AMPKα with shRNA specific for AMPKα blocked the protective effect of artemisinin.Similar results were obtained in primary cultured hippocampal neurons.Taken together,these results indicate that artemisinin can protect neuronal cells from oxidative damage,at least in part through the activation of AMPK.Because artemisinin is relatively inexpensive and has few side effects,our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.展开更多
目的观察青蒿素(artemisinin,ART)对脓毒症大鼠肺组织损伤的影响。方法采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)制作大鼠脓毒症模型,动物分为正常对照组、CLP组和青蒿素治疗(ART)组,分别于CLP术后2、6、12、24、48、72h活...目的观察青蒿素(artemisinin,ART)对脓毒症大鼠肺组织损伤的影响。方法采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)制作大鼠脓毒症模型,动物分为正常对照组、CLP组和青蒿素治疗(ART)组,分别于CLP术后2、6、12、24、48、72h活杀大鼠取肺组织,匀浆后动态浊度鲎试验法检测内毒素(lipopolysaccharide,LPS)水平,ELISA法检测TNF-α和IL-6的含量,实时荧光定量反转录聚合酶链反应(real-time RT-PCR)检测肺组织TNF-α和IL-6 mRNA的表达,光镜下观察肺组织的病理改变。结果CLP术后,ART组大鼠肺组织匀浆LPS、TNF-α和IL-6含量较CLP组明显降低(P<0.05,P<0.01),TNF-α和IL-6 mRNA的表达也显著低于CLP组(P<0.05,P<0.01),24h肺组织的病理损伤明显减轻。结论青蒿素可能通过降低脓毒症大鼠肺组织局部的LPS水平,抑制和减少了TNF-α和IL-6等促炎细胞因子的表达和释放,进而减轻肺组织的损伤。展开更多
基金National Natural Science Foundation of China(31771128)the University of Macao (MYRG2016-00052-FHS+2 种基金MYRG2018-00134-FHS)Science and Technology Development Fund (FDCT)of Macao (FDCT 021/2015/A1016/2016/A1).
文摘Oxidative stress is one of the main causes of neurodegenerative diseases such as Alzheimer disease(AD).Our previous studies have shown that artemisinin,a anti-malaria Chinese medicine,with neuroprotective effect,however,the antioxidative effect of artemisinin and its potential mechanism remain to be elucidated.In the present study,the protective effect and the underlying mechanism of artemisinin against injury of hydrogen peroxide(H_2O_2) in SH-SY5Y and hippocampal neurons were studied.Our results show that artemisinin protected SH-SY5Y and hippocampal neuronal cells from H_2O_2-induced cell death at clinically relevant concentrations in a concentration-dependent manner.Further studies showed that artemisinin significantly reduced cell death caused by H_2O_2 by restoring nuclear morphology,abnormal changes in intracellular ROS,activation of caspase 3,lactate dehydrogenase release and mitochondrial membrane potential.Hoechst staining and flow cytometry showed that artemisinin significantly reduced the apoptosis of SH-SY5Y cells exposed to H_2O_2.Western blotting analysis showed that artemisinin stimulated the phosphorylation and activation of AMP-activated protein kinase(AMPK) in SH-SY5Y cells in a time and concentration-dependent manner,whereas the application of AMPK inhibitor Compound C or decrease in expression of AMPKα with shRNA specific for AMPKα blocked the protective effect of artemisinin.Similar results were obtained in primary cultured hippocampal neurons.Taken together,these results indicate that artemisinin can protect neuronal cells from oxidative damage,at least in part through the activation of AMPK.Because artemisinin is relatively inexpensive and has few side effects,our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.
文摘拟探讨青蒿素抗鸡柔嫩艾美耳球虫(Eimeria tenella)的作用机制。将试验鸡随机分为空白对照组、攻毒对照组和青蒿素药物组,于攻毒后120h,收集试验鸡的盲肠并提取E.tenella第二代裂殖子。通过红细胞计数法计算第二代裂殖子数量;SYBR Green I荧光定量PCR检测第二代裂殖子微线基因(EtMIC1、EtMIC2、EtMIC3、EtMIC4、EtMIC5)mRNA相对转录量及扫描电镜观察试验鸡盲肠组织的病理学变化。结果表明:与攻毒对照组比较,青蒿素组的球虫第二代裂殖子数量降低了25.37%(P<0.05),同时裂殖子中微线基因EtMIC1、EtMIC2、EtMIC4的mRNA转录水平均显著下调(P<0.05),EtMIC3、EtMIC5则极显著下调(P<0.01);青蒿素组盲肠的病理组织结构也得到改善。青蒿素减轻鸡盲肠组织病变可能与其下调EtMICs mRNA转录并使裂殖子数量减少有关。
