TY - JOUR
T1 - Vincamine alleviates amyloid-β 25-35 peptides-induced cytotoxicity in PC12 cells
AU - Han, Jianfeng
AU - Qu, Qiumin
AU - Qiao, Jin
AU - Zhang, Jie
N1 - Publisher Copyright:
© 2017 Pharmacognosy Magazine Published by Wolters Kluwer Medknow.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Objective: Vincamine is a plant alkaloid used clinically as a peripheral vasodilator that increases cerebral blood flow and oxygen and glucose utilization by neural tissue to combat the effect of aging. The main purpose of the present study is to investigate the influence of vincamine on amyloid-β 25-35 (Aβ25-35) induced cytotoxicityto gain a better understanding of the neuroprotective effects of this clinically used anti-Alzheimer′s disease drug. Materials and Methods: Oxidative stress was assessed by measuring malondialdehydeglutathioneand superoxide dismutase (SOD) levels. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis detection was performed using an Annexin-V-FITC Apoptosis Detection Kit. The production of reactive oxygen species (ROS) was determined using an ROS Assay Kit. Western blot detection was carried out to detect the protein expression. Results: Our studies showed that pretreatment with vincamine could reduce Aβ25-35 induced oxidative stress. Vincamine markedly inhibited cell apoptosis dose-dependently. More importantlyvincamine increased the phosphatidylinositol-3 kinase (PI3K)/Akt and Bcl-2 family protein ratios on preincubation with cells for 2 h. Conclusion: Above observation led us to assume that one possible mechanism of vincamine protects Aβ25-35-induced cell death could be through upregulation of SOD and activation of the PI3K/Akt pathway. Abbreviation used: Aβ25-35: Amyloid-β 25-35; AD: Alzheimer′s disease; BCA: Bicinchoninic acid; GSH: glutathione; PBS: Phosphate buffered solution; SDS: Sodium dodecylsulphate; SOD: Superoxide dismutase Han Jianfeng 1 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Qu Qiumin 2 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Qiao Jin 3 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Zhang Jie 4 Institute of Liver Disease, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 Alzheimer's AssociationAlzheimer's disease facts and figures. Alzheimers Dement 2014;10:e47-92. Denk J, Boelmans K, Siegismund C, Lassner D, Arlt S, Jahn H, MicroRNA Profiling of CSF reveals potential biomarkers to detect Alzheimer's disease. PLoS One 20 1520;10:e0126423. Gandy S, DeKosky ST, Toward the treatment and prevention of Alzheimer's disease: Rational strategies and recent progress. Annu Rev Med 2013;64:367-83. Risacher SL, Saykin AJ, Neuroimaging and other biomarkers for Alzheimer's disease: The changing landscape of early detection. Annu Rev Clin Psychol 2013;9:621-48. Giacobini E, Gold G, Alzheimer disease therapy - Moving from amyloid-ß to tau. Nat Rev Neurol 2013;9:677-86. Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M, Alzheimer's disease: Clinical trials and drug development. Lancet Neurol 2010;9:702-16. Goure WF, Krafft GA, Jerecic J, Hefti F, Targeting the proper amyloid-beta neuronal toxins: A path forward for Alzheimer's disease immunotherapeutics. Alzheimers Res Ther 2014;6:42- Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 2008;14:837-42. Benilova I, Karran E, De Strooper B, The toxic Aßoligomer and Alzheimer's disease: An emperor in need of clothes. Nat Neurosci 2012;15:349-57. Narayan P, Holmström KM, Kim DH, Whitcomb DJ, Wilson MR, St George-Hyslop P, et al. Rare individual amyloid-ßoligomers act on astrocytes to initiate neuronal damage. Biochemistry 2014;53:2442-53. Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, et al. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer's amyloid-induced mitochondrial dysfunction. J Alzheimers Dis 2011;26:507-21. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 2008;14:1097-105. Takuma K, Yao J, Huang J, Xu H, Chen X, Luddy J, et al. ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. FASEB J 2005;19:597-8. Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, et al. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J Alzheimers Dis 2010;20:S535-50. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH, Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 2006;15:1437-49. Nie F, Liang Y, Xun H, Sun J, He F, Ma X, Inhibitory effects of tannic acid in the early stage of 3T3-L1 preadipocytes differentiation by down-regulating PPARg expression. Food Funct 2015;6:894-901. Jiang HZ, Quan XF, Tian WX, Hu JM, Wang PC, Huang SZ, et al. Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana. Bioorg Med Chem Lett 2010;20:6045-7. Quan X, Wang Y, Ma X, Liang Y, Tian W, Ma Q, et al. α-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase. PLoS One 2012;7:e33376- Liang Y, Tian W, Ma X, Inhibitory effects of grape skin extract and resveratrol on fatty acid synthase. BMC Complement Altern Med 2013;13:361- Zhao YX, Liang WJ, Fan HJ, Ma QY, Tian WX, Dai HF, et al. Fatty acid synthase inhibitors from the hulls of Nephelium lappaceum L. Carbohydr Res 2011;346:1302-6. Fan H, Wu D, Tian W, Ma X, Inhibitory effects of tannic acid on fatty acid synthase and 3T3-L1 preadipocyte. Biochim Biophys Acta 2013;1831:1260-6. Dany F, Liozon F, Goudoud JC, Castel JP, Michel JP, Marsaud P, et al. Severe ventricular arrhythmia following parenteral administration of vincamine. Predisposing factors in 6 cases. Arch Mal Coeur 1980;73:298-306. Lim CC, Cook PJ, James IM, The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers. Br J Clin Pharmacol 1980;9:100-1. Rassat J, Robenek H, Themann H, Changes in mouse hepatocytes caused by vincamin. A thin-sectioning and freeze-fracture study. Naunyn Schmiedebergs Arch Pharmacol 1982;318:349-57. Pesce E, Viganò V, Piacenza G, Effect of vincamine on platelet respiration. Farmaco Prat 1978;33:343-50. Fayed AH, Brain trace element concentration of rats treated with the plant alkaloid, vincamine. Biol Trace Elem Res 2010;136:314-9. Wang Y, Nie F, Ouyang J, Wang X, Ma X, Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells. Tumour Biol 2014;35:9563-9. Fan H, Tian W, Ma X, Curcumin induces apoptosis of HepG2 cells via inhibiting fatty acid synthase. Target Oncol 2014;9:279-86. Li P, Tian W, Wang X, Ma X, Inhibitory effect of desoxyrhaponticin and rhaponticin, two natural stilbene glycosides from the Tibetan nutritional food Rheum tanguticum Maxim. Ex Balf, on fatty acid synthase and human breast cancer cells. Food Funct 2014;5:251-6. Li P, Tian W, Ma X, Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer 2014;13:138- Small SA, Petsko GA, Retromer in Alzheimer disease, Parkinson disease and other neurological disorders. Nat Rev Neurosci 2015;16:126-32. Butterfield DA, Di Domenico F, Swomley AM, Head E, Perluigi M, Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: Overlaps in Down's syndrome and Alzheimer's disease brain. Biochem J 2014;463:177-89. Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol 2005;58:155-60. Esmaeili Tazangi P, Moosavi SM, Shabani M, Haghani M, Erythropoietin improves synaptic plasticity and memory deficits by decrease of the neurotransmitter release probability in the rat model of Alzheimer's disease.
AB - Objective: Vincamine is a plant alkaloid used clinically as a peripheral vasodilator that increases cerebral blood flow and oxygen and glucose utilization by neural tissue to combat the effect of aging. The main purpose of the present study is to investigate the influence of vincamine on amyloid-β 25-35 (Aβ25-35) induced cytotoxicityto gain a better understanding of the neuroprotective effects of this clinically used anti-Alzheimer′s disease drug. Materials and Methods: Oxidative stress was assessed by measuring malondialdehydeglutathioneand superoxide dismutase (SOD) levels. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis detection was performed using an Annexin-V-FITC Apoptosis Detection Kit. The production of reactive oxygen species (ROS) was determined using an ROS Assay Kit. Western blot detection was carried out to detect the protein expression. Results: Our studies showed that pretreatment with vincamine could reduce Aβ25-35 induced oxidative stress. Vincamine markedly inhibited cell apoptosis dose-dependently. More importantlyvincamine increased the phosphatidylinositol-3 kinase (PI3K)/Akt and Bcl-2 family protein ratios on preincubation with cells for 2 h. Conclusion: Above observation led us to assume that one possible mechanism of vincamine protects Aβ25-35-induced cell death could be through upregulation of SOD and activation of the PI3K/Akt pathway. Abbreviation used: Aβ25-35: Amyloid-β 25-35; AD: Alzheimer′s disease; BCA: Bicinchoninic acid; GSH: glutathione; PBS: Phosphate buffered solution; SDS: Sodium dodecylsulphate; SOD: Superoxide dismutase Han Jianfeng 1 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Qu Qiumin 2 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Qiao Jin 3 Department of Neurology, The First Clinical Hospital of Xian Jiaotong University, Xian 710061 Zhang Jie 4 Institute of Liver Disease, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 Alzheimer's AssociationAlzheimer's disease facts and figures. Alzheimers Dement 2014;10:e47-92. Denk J, Boelmans K, Siegismund C, Lassner D, Arlt S, Jahn H, MicroRNA Profiling of CSF reveals potential biomarkers to detect Alzheimer's disease. PLoS One 20 1520;10:e0126423. Gandy S, DeKosky ST, Toward the treatment and prevention of Alzheimer's disease: Rational strategies and recent progress. Annu Rev Med 2013;64:367-83. Risacher SL, Saykin AJ, Neuroimaging and other biomarkers for Alzheimer's disease: The changing landscape of early detection. Annu Rev Clin Psychol 2013;9:621-48. Giacobini E, Gold G, Alzheimer disease therapy - Moving from amyloid-ß to tau. Nat Rev Neurol 2013;9:677-86. Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M, Alzheimer's disease: Clinical trials and drug development. Lancet Neurol 2010;9:702-16. Goure WF, Krafft GA, Jerecic J, Hefti F, Targeting the proper amyloid-beta neuronal toxins: A path forward for Alzheimer's disease immunotherapeutics. Alzheimers Res Ther 2014;6:42- Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med 2008;14:837-42. Benilova I, Karran E, De Strooper B, The toxic Aßoligomer and Alzheimer's disease: An emperor in need of clothes. Nat Neurosci 2012;15:349-57. Narayan P, Holmström KM, Kim DH, Whitcomb DJ, Wilson MR, St George-Hyslop P, et al. Rare individual amyloid-ßoligomers act on astrocytes to initiate neuronal damage. Biochemistry 2014;53:2442-53. Dragicevic N, Smith A, Lin X, Yuan F, Copes N, Delic V, et al. Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer's amyloid-induced mitochondrial dysfunction. J Alzheimers Dis 2011;26:507-21. Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med 2008;14:1097-105. Takuma K, Yao J, Huang J, Xu H, Chen X, Luddy J, et al. ABAD enhances Abeta-induced cell stress via mitochondrial dysfunction. FASEB J 2005;19:597-8. Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, et al. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J Alzheimers Dis 2010;20:S535-50. Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH, Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 2006;15:1437-49. Nie F, Liang Y, Xun H, Sun J, He F, Ma X, Inhibitory effects of tannic acid in the early stage of 3T3-L1 preadipocytes differentiation by down-regulating PPARg expression. Food Funct 2015;6:894-901. Jiang HZ, Quan XF, Tian WX, Hu JM, Wang PC, Huang SZ, et al. Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana. Bioorg Med Chem Lett 2010;20:6045-7. Quan X, Wang Y, Ma X, Liang Y, Tian W, Ma Q, et al. α-Mangostin induces apoptosis and suppresses differentiation of 3T3-L1 cells via inhibiting fatty acid synthase. PLoS One 2012;7:e33376- Liang Y, Tian W, Ma X, Inhibitory effects of grape skin extract and resveratrol on fatty acid synthase. BMC Complement Altern Med 2013;13:361- Zhao YX, Liang WJ, Fan HJ, Ma QY, Tian WX, Dai HF, et al. Fatty acid synthase inhibitors from the hulls of Nephelium lappaceum L. Carbohydr Res 2011;346:1302-6. Fan H, Wu D, Tian W, Ma X, Inhibitory effects of tannic acid on fatty acid synthase and 3T3-L1 preadipocyte. Biochim Biophys Acta 2013;1831:1260-6. Dany F, Liozon F, Goudoud JC, Castel JP, Michel JP, Marsaud P, et al. Severe ventricular arrhythmia following parenteral administration of vincamine. Predisposing factors in 6 cases. Arch Mal Coeur 1980;73:298-306. Lim CC, Cook PJ, James IM, The effect of an acute infusion of vincamine and ethyl apovincaminate on cerebral blood flow in healthy volunteers. Br J Clin Pharmacol 1980;9:100-1. Rassat J, Robenek H, Themann H, Changes in mouse hepatocytes caused by vincamin. A thin-sectioning and freeze-fracture study. Naunyn Schmiedebergs Arch Pharmacol 1982;318:349-57. Pesce E, Viganò V, Piacenza G, Effect of vincamine on platelet respiration. Farmaco Prat 1978;33:343-50. Fayed AH, Brain trace element concentration of rats treated with the plant alkaloid, vincamine. Biol Trace Elem Res 2010;136:314-9. Wang Y, Nie F, Ouyang J, Wang X, Ma X, Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells. Tumour Biol 2014;35:9563-9. Fan H, Tian W, Ma X, Curcumin induces apoptosis of HepG2 cells via inhibiting fatty acid synthase. Target Oncol 2014;9:279-86. Li P, Tian W, Wang X, Ma X, Inhibitory effect of desoxyrhaponticin and rhaponticin, two natural stilbene glycosides from the Tibetan nutritional food Rheum tanguticum Maxim. Ex Balf, on fatty acid synthase and human breast cancer cells. Food Funct 2014;5:251-6. Li P, Tian W, Ma X, Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer 2014;13:138- Small SA, Petsko GA, Retromer in Alzheimer disease, Parkinson disease and other neurological disorders. Nat Rev Neurosci 2015;16:126-32. Butterfield DA, Di Domenico F, Swomley AM, Head E, Perluigi M, Redox proteomics analysis to decipher the neurobiology of Alzheimer-like neurodegeneration: Overlaps in Down's syndrome and Alzheimer's disease brain. Biochem J 2014;463:177-89. Tabert MH, Liu X, Doty RL, Serby M, Zamora D, Pelton GH, et al. A10-item smell identification scale related to risk for Alzheimer's disease. Ann Neurol 2005;58:155-60. Esmaeili Tazangi P, Moosavi SM, Shabani M, Haghani M, Erythropoietin improves synaptic plasticity and memory deficits by decrease of the neurotransmitter release probability in the rat model of Alzheimer's disease.
KW - Alzheimer's disease
KW - Amyloidβ
KW - PC12 cells
KW - Phosphatidylinositol-3 kinase/Akt pathway
KW - Vincamine
UR - https://www.scopus.com/pages/publications/85009727210
U2 - 10.4103/0973-1296.196309
DO - 10.4103/0973-1296.196309
M3 - 文章
AN - SCOPUS:85009727210
SN - 0973-1296
VL - 13
SP - 123
EP - 128
JO - Pharmacognosy Magazine
JF - Pharmacognosy Magazine
IS - 49
ER -