Dendrobium nobile Lindl.alkaloids(DNLA),the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons ag...Dendrobium nobile Lindl.alkaloids(DNLA),the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose deprivation.However,it is not clear whether DNLA reduces amyloid-beta(Aβ)-induced neuronal injury.In this study,cortical neurons were treated with DNLA at different concentrations(0.025,0.25,and 2.5 mg/L)for 24 hours,followed by administration of Aβ(25-35)(10μM).Aβ(25-35) treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial tumefaction.The damage caused by Aβ(25-35) on these cellular properties was markedly attenuated when cells were pretreated with DNLA.Treatment with Aβ(25-35)down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with DNLA.These findings suggest that DNLA reduces the cytotoxicity induced by Aβ(25-35) in rat primary cultured neurons.The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.展开更多
OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organel...OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organelles.Exposure to excessive manganese(Mn) causes neurotoxicity and can produce a Parkinson disease(PD)-like neurological disorder.Mitochondrial dysfunction and oxidative stress are implicated in the mechanism of Mn induced neurotoxicity.The present study was designed to determine whether Dendrobium nobile Lindl.alkaloids(DNLA),a Chinese medicinal herb extract,confers protective function over Mn-induced cell toxicity,and to investigate whether the modulation of PINK1/Parkin-mediated autophagy is involved in the mechanism of DNLA-mediated cell protection over Mn toxicity.METHODS AND RESULTS Rat adrenal pheochromocytoma PC12 cells were utilized as an in vitro model of Mn cell toxicity.It was found that the treatment of the PC12 cells with Mn resulted in concentration-dependent cell death,accompanied by a decrease in mitochondrial respiration capacity and an increase in ROS generation,whereas pretreatment of cells with DNLA significantly alleviated cell toxicity induced by Mn and improved mitochondrial function and oxidative status.Mn treatment enhanced apoptotic cells along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein.On the contrary,DNLA increased Bcl-2 expression,and concomitantly dramatically decreased the Bax/Bcl-2 ratio.Analysis of the expression of PINK1 and Parkin revealed that pretreatment of cells with DNLA significantly alleviated the decrease in protein levels of both PINK1 and Parkin caused by Mn.Furthermore,cells treated with Mn exhibited increased expression of LC3-Ⅱ and a decrease in accumulation of P62,which was noticeably reversed by the pretreatment of cells with DNLA.CONCLUSION DNLA inhibits Mn induced cytotoxicity,which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.展开更多
通过搜索Web of Science、PubMed和CNKI数据库中金钗石斛Dendrobium nobile的研究报道,对该植物的化学成分和药理作用的相关研究进行归纳总结。金钗石斛的化学成分主要包括生物碱、倍半萜、菲和联苄类等;药理作用主要表现在抗肿瘤、降...通过搜索Web of Science、PubMed和CNKI数据库中金钗石斛Dendrobium nobile的研究报道,对该植物的化学成分和药理作用的相关研究进行归纳总结。金钗石斛的化学成分主要包括生物碱、倍半萜、菲和联苄类等;药理作用主要表现在抗肿瘤、降血糖以及对神经系统保护等方面。在此基础上,进一步对金钗石斛化学成分的具体结构类型以及各类型的结构特征和波谱规律进行了梳理。有利于指导金钗石斛化学成分和药理作用的认识及研究,对该药食两用资源的深入开发利用提供参考依据。展开更多
基金financially supported by the National Natural Science Foundation of China,No.81473201the Natural Science Foundation of Educational Commission of Guizhou Province of China,No.2010043+1 种基金the Science and Technology Foundation of Guizhou Province of China,No.JZ[2014]2016the Modernization of Traditional Chinese Medicine Project of Guizhou Province of China,No.[2011]5086
文摘Dendrobium nobile Lindl.alkaloids(DNLA),the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose deprivation.However,it is not clear whether DNLA reduces amyloid-beta(Aβ)-induced neuronal injury.In this study,cortical neurons were treated with DNLA at different concentrations(0.025,0.25,and 2.5 mg/L)for 24 hours,followed by administration of Aβ(25-35)(10μM).Aβ(25-35) treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial tumefaction.The damage caused by Aβ(25-35) on these cellular properties was markedly attenuated when cells were pretreated with DNLA.Treatment with Aβ(25-35)down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with DNLA.These findings suggest that DNLA reduces the cytotoxicity induced by Aβ(25-35) in rat primary cultured neurons.The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.
文摘OBJECTIVE Activation of the PINK1/Parkin-mediated autophagy pathway has been proposed to play a protective role in the development of neurological disorders through the elimination of damaged macromolecules or organelles.Exposure to excessive manganese(Mn) causes neurotoxicity and can produce a Parkinson disease(PD)-like neurological disorder.Mitochondrial dysfunction and oxidative stress are implicated in the mechanism of Mn induced neurotoxicity.The present study was designed to determine whether Dendrobium nobile Lindl.alkaloids(DNLA),a Chinese medicinal herb extract,confers protective function over Mn-induced cell toxicity,and to investigate whether the modulation of PINK1/Parkin-mediated autophagy is involved in the mechanism of DNLA-mediated cell protection over Mn toxicity.METHODS AND RESULTS Rat adrenal pheochromocytoma PC12 cells were utilized as an in vitro model of Mn cell toxicity.It was found that the treatment of the PC12 cells with Mn resulted in concentration-dependent cell death,accompanied by a decrease in mitochondrial respiration capacity and an increase in ROS generation,whereas pretreatment of cells with DNLA significantly alleviated cell toxicity induced by Mn and improved mitochondrial function and oxidative status.Mn treatment enhanced apoptotic cells along with a marked increase in the protein expression of Bax and a decrease in the expression of Bcl-2 protein.On the contrary,DNLA increased Bcl-2 expression,and concomitantly dramatically decreased the Bax/Bcl-2 ratio.Analysis of the expression of PINK1 and Parkin revealed that pretreatment of cells with DNLA significantly alleviated the decrease in protein levels of both PINK1 and Parkin caused by Mn.Furthermore,cells treated with Mn exhibited increased expression of LC3-Ⅱ and a decrease in accumulation of P62,which was noticeably reversed by the pretreatment of cells with DNLA.CONCLUSION DNLA inhibits Mn induced cytotoxicity,which may be mediated through modulating PINK1/Parkin-mediated autophagic flux and improving mitochondrial function.
文摘通过搜索Web of Science、PubMed和CNKI数据库中金钗石斛Dendrobium nobile的研究报道,对该植物的化学成分和药理作用的相关研究进行归纳总结。金钗石斛的化学成分主要包括生物碱、倍半萜、菲和联苄类等;药理作用主要表现在抗肿瘤、降血糖以及对神经系统保护等方面。在此基础上,进一步对金钗石斛化学成分的具体结构类型以及各类型的结构特征和波谱规律进行了梳理。有利于指导金钗石斛化学成分和药理作用的认识及研究,对该药食两用资源的深入开发利用提供参考依据。