淫羊藿苷在阿尔茨海默病中的神经保护作用及机制研究进展
|
摘要
阿尔茨海默病(AD)是一种以认知功能障碍为主要特征的神经退行性疾病,目前尚缺乏有效治疗药物。根据中医理论与实验研究发现,补肾壮阳药淫羊藿对AD有一定治疗作用,而其有效成分淫羊藿苷可通过作用于多个靶点,在AD治疗中发挥重要作用。本文主要就近几年国内外研究的相关文献,对淫羊藿苷治疗AD的作用机制进行分析并阐述。
Alzheimer's disease( AD) is a neurodegenerative disease characterized by cognitive dysfunction,with no effective treatment at present.According to the theory and experimental research of Chinese medicine,Bushenzhuangyang medicine Epimedium has certain therapeutic effects on AD. Its active ingredient icariin may play an important role in the treatment of AD by acting on multiple targets. In this paper,the related literatures of domestic and foreign research in recent years are studied to analyze and explain the mechanism of action of icariin in the Epimedium treatment of AD.
Alzheimer's disease( AD) is a neurodegenerative disease characterized by cognitive dysfunction,with no effective treatment at present.According to the theory and experimental research of Chinese medicine,Bushenzhuangyang medicine Epimedium has certain therapeutic effects on AD. Its active ingredient icariin may play an important role in the treatment of AD by acting on multiple targets. In this paper,the related literatures of domestic and foreign research in recent years are studied to analyze and explain the mechanism of action of icariin in the Epimedium treatment of AD.
引文
[1]Duarte A I, Santos M S, Oliveira C R, et al. Brain insulin signalling, glucose metabolism and females' reproductive aging: A dangerous triad in Alzheimer's disease . Neuropharmacology, 2018,136(Pt B)∶223～242.
[2]Kumar D, Ganeshpurkar A, Kumar D, et al. Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead . Eur J Med Chem, 2018, 148(15)∶436～452.
[3]Kametani F, Hasegawa M. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease. Front Neurosci, 2018, 12(30)∶95～102.
[4]Doody R S, Thomas R G, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease . N Engl J Med, 2014, 370(4)∶311～321.
[5]De La Torre J C. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. N Engl J Med, 2014, 370(15)∶1459～1460.
[6]Hung S Y, Fu W M. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci, 2017, 24(1)∶47.
[7]Lyon J. Alzheimer Outlook Far From Bleak. Jama, 2017, 317(9)∶896～898.
[8]Atri A, Fr?lich L, Ballard C, et al. Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials. Jama, 2018, 319(2)∶130～142.
[9]张紫嫣, 黄雅薇, 张新雪, 等. "肾髓系统"的理论渊源. 世界科学技术-中医药现代化, 2017, 19(5)∶744～748.
[10]许玉珉, 章时杰, 王馨晨,等. 补肾益智方对Aβ25-35致阿尔茨海默病小鼠空间学习记忆及细胞凋亡机制的研究 . 中药药理与临床, 2018,34(1)∶127～130.
[11]Li C, Li Q, Mei Q, et al. Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii . Life Sciences, 2015, 126∶57～68.
[12]Yang W T, Zheng X W, Chen S, et al. Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis . Biochem Pharmacol, 2017, 141∶143～155.
[13]Nie J, Luo Y, Huang X N, et al. Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus . Eur J Pharmacol, 2010, 626(2-3)∶213～218.
[14]Sheng C, Xu P, Zhou K, et al. Icariin Attenuates Synaptic and Cognitive Deficits in an Abeta1-42-Induced Rat Model of Alzheimer's Disease . Biomed Res Int, 2017, 2017∶27464872.
[15]王梅玲. 淫羊藿苷对阿尔茨海默病炎症模型大鼠神经细胞的保护作用 . 中药药理与临床, 2014,30(1):42～46.
[16]Urano T, Tohda C. Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid beta-induced neurite atrophy . Phytother Res, 2010, 24(11)∶1658～1663.
[17]Zhang Z, Zhang T, Dong K. Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence- accelerated mouse . Neural Regen Res, 2012, 7(12)∶885～890.
[18]Gao L, Tang Q, He X, et al. Effect of icariin on learning and memory abilities and activity of cholinergic system of senescence-accelerated mice SAMP10 . Zhongguo Zhong Yao Za Zhi, 2012, 37(14)∶2117～2121.
[19]Jin F, Gong Q H, Xu Y S, et al. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling . Int J Neuropsychopharmacol, 2014, 17(6)∶871～881.
[20]Zhang Z Y, Li C, Zug C, et al. Icariin ameliorates neuropathological changes, TGF-beta1 accumulation and behavioral deficits in a mouse model of cerebral amyloidosis . PLoS One, 2014, 9(8)∶2e104616.
[21]Zhang L, Shen C, Chu J, et al. Icariin decreases the expression of APP and BACE-1 and reduces the beta-amyloid burden in an APP transgenic mouse model of Alzheimer's disease . Int J Biol Sci, 2014, 10(2)∶181～191.
[22]Li F, Dong H X, Gong Q H, et al. Icariin decreases both APP and Abeta levels and increases neurogenesis in the brain of Tg2576 mice . Neuroscience, 2015, 304∶29～35.
[23]Chen Y J, Zheng H Y, Huang X X, et al. Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice . CNS Neurosci Ther, 2016, 22(1)∶63～73.
[24]Chen Y, Han S, Huang X, et al. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3x Tg-AD Mice . Int J Mol Sci, 2016, 17(2)∶163.
[25]Majd S, Power J H T. Oxidative Stress and Decreased Mitochondrial Superoxide Dismutase 2 and Peroxiredoxin 1 and 4 Based Mechanism of Concurrent Activation of AMPK and mTOR in Alzheimer's disease . Curr Alzheimer Res, 2018, 15(8)∶764～776.
[26]Cardoso S, Seica R, Moreira P I. Diabesity and Brain Energy Metabolism: The Case of Alzheimer's Disease . Adv Neurobiol, 2017, 19∶117～150.
[27]Kapogiannis D, Mattson M P. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease . Lancet Neurology, 2011, 10(2)∶187～198.
[28]Huang N Q, Jin H, Zhou S Y, et al. TLR4 is a link between diabetes and Alzheimer's disease . Behav Brain Res, 2017, 316∶234～244.
[29]张晓菲,路畅,贺晓丽,等.淫羊藿苷预防给药对快速老化小鼠SAMP8学习记忆能力及脑组织线粒体氧化应激的影响 .中国药理学通报,2015,31(7)∶925～930.
[30]吴满刚,贺晓丽,强桂芬,等.淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用 .中国临床药理学与治疗学,2010,15(7)∶721～726.
[31]Zhang Y, Kong W N, Chai X Q. Compound of icariin, astragalus, and puerarin mitigates iron overload in the cerebral cortex of Alzheimer's disease mice . Neural Regen Res, 2018, 13(4)∶731～736.
[32]Li W W, Gao X M, Wang X M, et al. Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity . Mutat Res, 2011, 708(1-2)∶1～10.
[33]Zong N, Li F, Deng Y, et al. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus . Behav Brain Res, 2016, 313∶111～119.
[34]Zeng K W, Ko H, Yang H O, et al. Icariin attenuates beta-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells . Neuropharmacology, 2010, 59(6)∶542～550.
[35]Zhang D, Wang Z, Sheng C, et al. Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells . Evid Based Complement Alternat Med, 2015, 2015∶2235265.
[36]Salter M W, Beggs S. Sublime microglia∶2expanding roles for the guardians of the CNS . Cell, 2014, 158(1)∶15～24.
[37]Zeng K W, Fu H, Liu G X, et al. Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-kappaB and JNK/p38 MAPK pathways . Int Immunopharmacol, 2010, 10(6)∶668～678.
[38]Wang G Q, Li D D, Huang C, et al. Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro . Front Mol Neurosci, 2018, 10∶441.
[39]金凤, 陈晨, 金海, 等. 淫羊藿苷通过抑制TNF-α,IL-6和caspase-3的表达改善Aβ25-35诱导的阿茨海默病大鼠空间学习记忆能力 . 中国新药与临床杂志, 2013,32(10)∶833～837.
[40]王冉, 方芳. 自噬在阿尔茨海默病中的作用及药物干预研究进展 . 中国药学杂志, 2015, 50(5)∶381～385.
[41]Nixon R A, Yang D S. Autophagy Failure in Alzheimer's Disease - Locating the Primary Defect . Neurobiology of Disease, 2011,43(1)∶38～45.
[42]Loos B, Klionsky D J, Wong E. Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging . Progress in Neurobiology, 2017, 156∶90～106.
[43]Wolfe D M, Lee J H, Kumar A, et al. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification . European Journal of Neuroscience, 2013, 37(12)∶1949～1961.
[44]Jiang S, Chang H, Deng S, et al. Icariin inhibits autophagy and promotes apoptosis in SKVCR cells through mTOR signal pathway . Cell Mol Biol (Noisy-le-grand), 2018, 64(6)∶4～10.
[45]Mo Z T, Li W N, Zhai Y R, et al. Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between Apoptosis and Autophagy in PC12 Cells . Evid Based Complement Alternat Med, 2016, 2016∶4343084.
[46]Zhang Y, Huang N Q, Yan F, et al. Diabetes mellitus and Alzheimer's disease: GSK-3beta as a potential link. Behav Brain Res, 2018, 339∶57～65.
[47]More S V, Kumar H, Cho D Y, et al. Toxin-Induced Experimental Models of Learning and Memory Impairment. Int J Mol Sci, 2016, 17(9)∶1447.
[48]罗勇, 聂晶, 龚其海, 等. 淫羊藿苷减轻铝诱导的大鼠学习记忆减退并增强皮质及海马Na+-K+-ATPase、Ca2+-ATPase活性 . 中药药理与临床, 2008, 24(3)∶24～25.
[2]Kumar D, Ganeshpurkar A, Kumar D, et al. Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead . Eur J Med Chem, 2018, 148(15)∶436～452.
[3]Kametani F, Hasegawa M. Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease. Front Neurosci, 2018, 12(30)∶95～102.
[4]Doody R S, Thomas R G, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease . N Engl J Med, 2014, 370(4)∶311～321.
[5]De La Torre J C. Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease. N Engl J Med, 2014, 370(15)∶1459～1460.
[6]Hung S Y, Fu W M. Drug candidates in clinical trials for Alzheimer's disease. J Biomed Sci, 2017, 24(1)∶47.
[7]Lyon J. Alzheimer Outlook Far From Bleak. Jama, 2017, 317(9)∶896～898.
[8]Atri A, Fr?lich L, Ballard C, et al. Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease: Three Randomized Clinical Trials. Jama, 2018, 319(2)∶130～142.
[9]张紫嫣, 黄雅薇, 张新雪, 等. "肾髓系统"的理论渊源. 世界科学技术-中医药现代化, 2017, 19(5)∶744～748.
[10]许玉珉, 章时杰, 王馨晨,等. 补肾益智方对Aβ25-35致阿尔茨海默病小鼠空间学习记忆及细胞凋亡机制的研究 . 中药药理与临床, 2018,34(1)∶127～130.
[11]Li C, Li Q, Mei Q, et al. Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii . Life Sciences, 2015, 126∶57～68.
[12]Yang W T, Zheng X W, Chen S, et al. Chinese herbal medicine for Alzheimer's disease: Clinical evidence and possible mechanism of neurogenesis . Biochem Pharmacol, 2017, 141∶143～155.
[13]Nie J, Luo Y, Huang X N, et al. Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus . Eur J Pharmacol, 2010, 626(2-3)∶213～218.
[14]Sheng C, Xu P, Zhou K, et al. Icariin Attenuates Synaptic and Cognitive Deficits in an Abeta1-42-Induced Rat Model of Alzheimer's Disease . Biomed Res Int, 2017, 2017∶27464872.
[15]王梅玲. 淫羊藿苷对阿尔茨海默病炎症模型大鼠神经细胞的保护作用 . 中药药理与临床, 2014,30(1):42～46.
[16]Urano T, Tohda C. Icariin improves memory impairment in Alzheimer's disease model mice (5xFAD) and attenuates amyloid beta-induced neurite atrophy . Phytother Res, 2010, 24(11)∶1658～1663.
[17]Zhang Z, Zhang T, Dong K. Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence- accelerated mouse . Neural Regen Res, 2012, 7(12)∶885～890.
[18]Gao L, Tang Q, He X, et al. Effect of icariin on learning and memory abilities and activity of cholinergic system of senescence-accelerated mice SAMP10 . Zhongguo Zhong Yao Za Zhi, 2012, 37(14)∶2117～2121.
[19]Jin F, Gong Q H, Xu Y S, et al. Icariin, a phosphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling . Int J Neuropsychopharmacol, 2014, 17(6)∶871～881.
[20]Zhang Z Y, Li C, Zug C, et al. Icariin ameliorates neuropathological changes, TGF-beta1 accumulation and behavioral deficits in a mouse model of cerebral amyloidosis . PLoS One, 2014, 9(8)∶2e104616.
[21]Zhang L, Shen C, Chu J, et al. Icariin decreases the expression of APP and BACE-1 and reduces the beta-amyloid burden in an APP transgenic mouse model of Alzheimer's disease . Int J Biol Sci, 2014, 10(2)∶181～191.
[22]Li F, Dong H X, Gong Q H, et al. Icariin decreases both APP and Abeta levels and increases neurogenesis in the brain of Tg2576 mice . Neuroscience, 2015, 304∶29～35.
[23]Chen Y J, Zheng H Y, Huang X X, et al. Neuroprotective Effects of Icariin on Brain Metabolism, Mitochondrial Functions, and Cognition in Triple-Transgenic Alzheimer's Disease Mice . CNS Neurosci Ther, 2016, 22(1)∶63～73.
[24]Chen Y, Han S, Huang X, et al. The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3x Tg-AD Mice . Int J Mol Sci, 2016, 17(2)∶163.
[25]Majd S, Power J H T. Oxidative Stress and Decreased Mitochondrial Superoxide Dismutase 2 and Peroxiredoxin 1 and 4 Based Mechanism of Concurrent Activation of AMPK and mTOR in Alzheimer's disease . Curr Alzheimer Res, 2018, 15(8)∶764～776.
[26]Cardoso S, Seica R, Moreira P I. Diabesity and Brain Energy Metabolism: The Case of Alzheimer's Disease . Adv Neurobiol, 2017, 19∶117～150.
[27]Kapogiannis D, Mattson M P. Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease . Lancet Neurology, 2011, 10(2)∶187～198.
[28]Huang N Q, Jin H, Zhou S Y, et al. TLR4 is a link between diabetes and Alzheimer's disease . Behav Brain Res, 2017, 316∶234～244.
[29]张晓菲,路畅,贺晓丽,等.淫羊藿苷预防给药对快速老化小鼠SAMP8学习记忆能力及脑组织线粒体氧化应激的影响 .中国药理学通报,2015,31(7)∶925～930.
[30]吴满刚,贺晓丽,强桂芬,等.淫羊藿苷对快速老化小鼠SAMP8脑线粒体的保护作用 .中国临床药理学与治疗学,2010,15(7)∶721～726.
[31]Zhang Y, Kong W N, Chai X Q. Compound of icariin, astragalus, and puerarin mitigates iron overload in the cerebral cortex of Alzheimer's disease mice . Neural Regen Res, 2018, 13(4)∶731～736.
[32]Li W W, Gao X M, Wang X M, et al. Icariin inhibits hydrogen peroxide-induced toxicity through inhibition of phosphorylation of JNK/p38 MAPK and p53 activity . Mutat Res, 2011, 708(1-2)∶1～10.
[33]Zong N, Li F, Deng Y, et al. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus . Behav Brain Res, 2016, 313∶111～119.
[34]Zeng K W, Ko H, Yang H O, et al. Icariin attenuates beta-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells . Neuropharmacology, 2010, 59(6)∶542～550.
[35]Zhang D, Wang Z, Sheng C, et al. Icariin Prevents Amyloid Beta-Induced Apoptosis via the PI3K/Akt Pathway in PC-12 Cells . Evid Based Complement Alternat Med, 2015, 2015∶2235265.
[36]Salter M W, Beggs S. Sublime microglia∶2expanding roles for the guardians of the CNS . Cell, 2014, 158(1)∶15～24.
[37]Zeng K W, Fu H, Liu G X, et al. Icariin attenuates lipopolysaccharide-induced microglial activation and resultant death of neurons by inhibiting TAK1/IKK/NF-kappaB and JNK/p38 MAPK pathways . Int Immunopharmacol, 2010, 10(6)∶668～678.
[38]Wang G Q, Li D D, Huang C, et al. Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro . Front Mol Neurosci, 2018, 10∶441.
[39]金凤, 陈晨, 金海, 等. 淫羊藿苷通过抑制TNF-α,IL-6和caspase-3的表达改善Aβ25-35诱导的阿茨海默病大鼠空间学习记忆能力 . 中国新药与临床杂志, 2013,32(10)∶833～837.
[40]王冉, 方芳. 自噬在阿尔茨海默病中的作用及药物干预研究进展 . 中国药学杂志, 2015, 50(5)∶381～385.
[41]Nixon R A, Yang D S. Autophagy Failure in Alzheimer's Disease - Locating the Primary Defect . Neurobiology of Disease, 2011,43(1)∶38～45.
[42]Loos B, Klionsky D J, Wong E. Augmenting brain metabolism to increase macro- and chaperone-mediated autophagy for decreasing neuronal proteotoxicity and aging . Progress in Neurobiology, 2017, 156∶90～106.
[43]Wolfe D M, Lee J H, Kumar A, et al. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification . European Journal of Neuroscience, 2013, 37(12)∶1949～1961.
[44]Jiang S, Chang H, Deng S, et al. Icariin inhibits autophagy and promotes apoptosis in SKVCR cells through mTOR signal pathway . Cell Mol Biol (Noisy-le-grand), 2018, 64(6)∶4～10.
[45]Mo Z T, Li W N, Zhai Y R, et al. Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between Apoptosis and Autophagy in PC12 Cells . Evid Based Complement Alternat Med, 2016, 2016∶4343084.
[46]Zhang Y, Huang N Q, Yan F, et al. Diabetes mellitus and Alzheimer's disease: GSK-3beta as a potential link. Behav Brain Res, 2018, 339∶57～65.
[47]More S V, Kumar H, Cho D Y, et al. Toxin-Induced Experimental Models of Learning and Memory Impairment. Int J Mol Sci, 2016, 17(9)∶1447.
[48]罗勇, 聂晶, 龚其海, 等. 淫羊藿苷减轻铝诱导的大鼠学习记忆减退并增强皮质及海马Na+-K+-ATPase、Ca2+-ATPase活性 . 中药药理与临床, 2008, 24(3)∶24～25.