芍药苷干预阿尔茨海默病作用机制研究进展
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摘要
阿尔茨海默病(Alzheimer’sdisease,AD)是造成老龄人口认知能力减退的主要疾病之一。芍药苷是毛茛科(Ranunculaceae)植物芍药Paeonia lactiflora或牡丹Paeonia suffruticosa根皮中提取出的水溶性单萜苷,具有改善认知能力、镇静、抗炎、镇痛、解痉等作用,可以有效调节AD动物及细胞模型异常磷酸化的Tau蛋白和过度沉积的β-淀粉样蛋白(Aβ)水平,恢复乙酰胆碱、神经生长因子、Ca2+、α7烟碱样乙酰胆碱受体和腺苷受体等神经递质及神经受体的平衡状态,降低组织炎症反应和氧化应激反应并减少细胞凋亡的发生。对近10年来国内外有关芍药苷干预AD的研究进展进行综述,为探索中药防治AD研究提供理论依据。
Alzheimer's disease(AD) is one of the main pathogenies of the cognitive decline in aging population. Paeoniflorin is a water-soluble monoterpene isolated from the roots of Paeonia lactiflora or P. suffruticosa, which are both in the family Ranunculaceae. Paeoniflorin has the effect of improving the cognitive ability, sedative, anti-inflammatory, analgesic, and spasmolytisch activities. It could also regulate hyperphosphorylation of Tau and Aβ proteins; Paeoniflorin can restore the balance of neurotransmitter and neurotransmitter receptors including acetylcholine, nerve growth factor, calcium ion, α7 nicotinic acetylcholine receptor and adenosine receptors, and reduce inflammation, oxidative stress and neuron apoptosis in AD animal and cell models. This paper reviewed relevant research in the past decade about the effect of paeoniflorin on AD, which may provide theoretical basis to use agent from Chinese medicine for AD prevention and treatment.
Alzheimer's disease(AD) is one of the main pathogenies of the cognitive decline in aging population. Paeoniflorin is a water-soluble monoterpene isolated from the roots of Paeonia lactiflora or P. suffruticosa, which are both in the family Ranunculaceae. Paeoniflorin has the effect of improving the cognitive ability, sedative, anti-inflammatory, analgesic, and spasmolytisch activities. It could also regulate hyperphosphorylation of Tau and Aβ proteins; Paeoniflorin can restore the balance of neurotransmitter and neurotransmitter receptors including acetylcholine, nerve growth factor, calcium ion, α7 nicotinic acetylcholine receptor and adenosine receptors, and reduce inflammation, oxidative stress and neuron apoptosis in AD animal and cell models. This paper reviewed relevant research in the past decade about the effect of paeoniflorin on AD, which may provide theoretical basis to use agent from Chinese medicine for AD prevention and treatment.
引文
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[27]Gu X Y,Cai Z X,Cai M,et al.Protective effect of paeoniflorin on inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of Alzheimer's disease[J].Mol Med Rep,2016,13(3):2247-2252.
[28]Liu H Y,Wang J Y,Wang J,et al.Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB and VEGF/Flt-1 signaling pathways[J].Brain Res,2015,doi:10.1016/j.brainres.2015.05.035.
[29]Cheignon C,Tomas M,Bonnefont-Rousselotc D,et al.Oxidative stress and the amyloid beta peptide in Alzheimer’s disease[J].Redox Biol,2018,doi:10.1016/j.redox.2017.10.014.
[30]郭春燕,罗强,孙黎,等.芍药苷对H2O2诱导SH-SY5Y神经细胞损伤的保护作用[J].中草药,2013,44(20):2864-2871.
[31]Wang K,Zhu L,Zhu X,et al.Protective effect of paeoniflorin on Aβ25-35-induced SH-SY5Y cell injury by preventing mitochondrial dysfunction[J].Cell Mol Neurobiol,2014,34(2):227-234.
[32]Wang Y,Liu T,Pan W,et al.Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aβ1-42expression[J].Exp Ther Med,2016,11(2):593-600.
[33]Shoshan-Barmatz V,Nahon-Crystal E,Shteinfer-Kuzmine A,et al.VDAC1,mitochondrial dysfunction,and Alzheimer’s disease[J].Pharm Res,2018,doi:10.1016/j.phrs.2018.03.010.
[34]Sun R,Wang K,Wu D D,et al.Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway[J].Folia Neuropathol,2012,50(3):270-276.
[2]Nelson P T,Alafuzoff I,Bigi E H,et al.Correlation of Alzheimer disease neuropathologic changes with cognitive status:A review of the literature[J].JNeuropathol Exper Neurol,2012,71(5):362-381.
[3]Rempe R G,Hartz A M S,Bauer B.Matrix metalloproteinases in the brain and blood-brain barrier:Versatile breakers and makers[J].J Cerebr Blood F Met,2016,36(9):1481-1507.
[4]中国药典[S].一部.2015.
[5]张东方,税丕先,高红莉,等.生药学[M].北京:中国医药科学出版社,2016.
[6]Fu X,Wang Q H,Wang Z B,et al.Danggui-ShaoyaoSan:New hope for Alzheimer’s disease[J].Aging Disease,2016,7(4):502-513.
[7]毛敬洁,陈亚萍,林如辉,等.小续命汤对APP/PS1转基因鼠海马区Aβ、GFAP蛋白的影响及其行为学分析[J].康复学报,2016,26(4):28-33.
[8]Hou X Q,Wu D W,Zhang C X,et al.Bushen-Yizhi formula ameliorates cognition deficits and attenuates oxidative stress-related neuronal apoptosis in scopolamine-induced senescence in mice[J].Inter J Mol Med,2014,34(2):429-439.
[9]Wang Y,Mandelkow E.Tau in physiology and pathology[J].Nate Rev Neur,2016,17(1):5-21.
[10]Ma X H,Duan W J,Mo Y S,et al.Neuroprotective effect of paeoniflorin on okadaic acid-induced tau hyperphosphorylation via calpain/Akt/GSK-3 beta pathway in SH-SY5Y cells[J].Brain Res,2018,doi:10.1016/j.brainres.2018.03.022.
[11]Jiang T,Yu J T,Zhu X C,et al.Temsirolimus attenuates tauopathy in vitro and in vivo by targeting tau hyperphosphorylation and autophagic clearance[J].Neuropharmacology,2014,doi:10.1016/j.neuropharm.2014.05.032.
[12]朱燃,黄田喜,赵雪梅,等.10种中草药成分对体外过表达Aβ的影响及机制探讨[J].药学学报,2014,49(6):800-806.
[13]周楠楠,朱燃,赵雪梅,等.天麻素、黄芪总皂苷和芍药苷对阿尔茨海默病模型小鼠脑内β淀粉样多肽表达的影响及其机制[J].中华病理学杂志,2016,45(11):780-784.
[14]Zhou L,Chen L,Fu Q,et al.Paeoniflorin attenuates amyloid-beta peptide-induced neurotoxicity by ameliorating oxidative stress and regulating the NGF-mediated signaling in rats[J].Brain Res,2013,doi:10.1016/j.brainres.2012.12.040.
[15]Li A P,Yang F,Song J,et al.Inhibition of Abeta proteotoxicity by paeoniflorin in Caenorhabditis elegans through regulation of oxidative and heat shock stress responses[J].Rejuv Res,2018,21(4):304-312.
[16]Ferreira-Vieira T H,Guimaraes I M,Silva F R,et al.Alzheimer’s disease:Targeting the cholinergic system[J].Curr Neuropharmacol,2016,doi:10.2174/1570159X13666150716165726.
[17]Niewiadomska G,Mietelska-Porowska A,Mazurkiewicz M.The cholinergic system,nerve growth factor and the cytoskeleton[J].Behav Brain Res,2011,221(2):515-526.
[18]Williams B J,Eriksdotter-Jonhagen M,Granholm A C.The intersection of NGF/TrkA signaling and amyloid precursor protein processing in Alzheimer’s disease neuropathology[J].Inter J Mol Sci,2017,doi:10.1111/j.1471-4159.2005.03181.x.
[19]Popugaeva E,Pchitskaya E,Bezprozvanny I.Dysregulation of neuronal calcium homeostasis in Alzheimer’s disease-a therapeutic opportunity?[J].Biochem Biophysical Res Commun,2017,483(4):998-1004.
[20]马伟,马卫东,苗珍花,等.芍药苷神经保护作用的实验研究[J].宁夏医科大学学报,2011,33(2):132-135.
[21]Zhong S Z,Ge Q H,Li Q,et al.Peoniflorin attentuates Aβ1-42-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats[J].J Neurol Sci,2009,280(1/2):71-78.
[22]Yakel J L.Nicotinic Ach receptors in the hippocampal circuit;functional expression and role in synaptic plasticity[J].J Physiol,2014,592(19):4147-4153.
[23]Gomes C V,Kaster M P,ToméA R,et al.Adenosine receptors and brain diseases:Neuroprotection and neurodegeneration[J].BBA-Biomembranes,2011,1808(5):1380-1399.
[24]闫蓉.JD-30主要成分芍药苷和芍药内酯苷的神经保护作用及机制研究[D].广州:广州中医药大学,2014.
[25]Laurent C,Buée L,Blum D.Tau and neuroinflammation:What impact for Alzheimer’s disease and tauopathies?[J].Biomed J,2018,41(1):21-33.
[26]Zhang H R,Peng J H,Cheng X B,et al.Paeoniflorin atttenuates amyloidogenesis and the inflammatory responses in a transgenic mouse model of Alzheimer’s disease[J].Neurochem Res,2015,40(8):1583-1592.
[27]Gu X Y,Cai Z X,Cai M,et al.Protective effect of paeoniflorin on inflammation and apoptosis in the cerebral cortex of a transgenic mouse model of Alzheimer's disease[J].Mol Med Rep,2016,13(3):2247-2252.
[28]Liu H Y,Wang J Y,Wang J,et al.Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB and VEGF/Flt-1 signaling pathways[J].Brain Res,2015,doi:10.1016/j.brainres.2015.05.035.
[29]Cheignon C,Tomas M,Bonnefont-Rousselotc D,et al.Oxidative stress and the amyloid beta peptide in Alzheimer’s disease[J].Redox Biol,2018,doi:10.1016/j.redox.2017.10.014.
[30]郭春燕,罗强,孙黎,等.芍药苷对H2O2诱导SH-SY5Y神经细胞损伤的保护作用[J].中草药,2013,44(20):2864-2871.
[31]Wang K,Zhu L,Zhu X,et al.Protective effect of paeoniflorin on Aβ25-35-induced SH-SY5Y cell injury by preventing mitochondrial dysfunction[J].Cell Mol Neurobiol,2014,34(2):227-234.
[32]Wang Y,Liu T,Pan W,et al.Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aβ1-42expression[J].Exp Ther Med,2016,11(2):593-600.
[33]Shoshan-Barmatz V,Nahon-Crystal E,Shteinfer-Kuzmine A,et al.VDAC1,mitochondrial dysfunction,and Alzheimer’s disease[J].Pharm Res,2018,doi:10.1016/j.phrs.2018.03.010.
[34]Sun R,Wang K,Wu D D,et al.Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway[J].Folia Neuropathol,2012,50(3):270-276.