RSS-Feed abonnieren
DOI: 10.1055/s-0031-1299763
Protective Effect of Puerarin on β-Amyloid-Induced Neurotoxicity in Rat Hippocampal Neurons
Publikationsverlauf
received 22. November 2011
accepted 14. Dezember 2011
Publikationsdatum:
25. Januar 2012 (online)
![](https://www.thieme-connect.de/media/amf/201204/lookinside/thumbnails/10.1055-s-0031-1299763-1.jpg)
Abstract
Puerarin (CAS Number 3681-99-0), a major isoflavone glycoside purified from Pueraria lobata, was reported to posses antioxidative and estrogen-like biological activities. Recent studies showed that puerarin protects different cell types from damage caused by a variety of toxic stimuli. In the present study, we investigated the neuroprotective effect of puerarin against Aβ25–35-induced neurotoxicity in cultured hippocampal neurons, as well as the underlying mechanism(s). Following exposure of cells to Aβ25–35, cell survival and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were reduced while production of reactive oxygen species (ROS) was increased. Preincubation of the cells with puerarin prior to Aβ25–35 exposure increased cell survival and GSH-Px and CAT activities and decreased ROS production. It was previously shown that overactivation of glycogen synthase kinase-3β (GSK-3β) is implicated in Aβ-induced cell death. In this study, Aβ25–35 treatment is found to increase GSK-3β activity and pretreatment with puerarin preventesAβ-induced activation of GSK-3β based on Western blot analysis. In addition, puerarin is shown to activate protein kinase B (PKB)/Akt, an important upstream kinase of GSK-3β, possibly promoting subsequent GSK-3β inhibition. Our data suggest that puerarin attenuates cell death induced by Aβ25–35 via various mechanisms, which might be beneficial for the treatment of Alzheimer’s disease.
Key words
puerarin (3681-99-0) - alzheimer’s disease - oxidative stress - glycogen synthase kinase-3β - protein kinase B* These 2 authors contributed equally to this work (co-first author).
-
References
- 1 Selkoe DJ. Toward a comprehensive theory for Alzheimer’s disease. Hypothesis: Alzheimer’s disease is caused by the cerebral accumulation and cytotoxicity of amyloid beta-protein. Ann N Y Acad Sci 2000; 924: 17-25
- 2 Koo EH, Lansbury Jr PT, Kelly JW. Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci USA 1999; 96: 9989-9990
- 3 Hardy J. Alzheimer’s disease: the amyloid cascade hypothesis: an update and reappraisal. J Alzheimers Dis 2006; 9: 151-153
- 4 Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997; 23: 134-147
- 5 Luo YQ, Hirashima N, Li YH et al. Physiological levels of beta-amyloid increase tyrosine phosphorylation and cytosolic calcium. Brain Res 1995; 681: 65-74
- 6 Canzoniero LM, Snider BJ. Calcium in Alzheimer’s disease pathogenesis: too much, too little or in the wrong place?. J Alzheimers Dis 2005; 8: 147-154
- 7 Qicheng F. Some current study and research approaches relating to the use of plants in the traditional Chinese medicine. J Ethnopharmacol 1980; 2: 57-63
- 8 Fan LL, Sun LH, Li J et al. The protective effect of puerarin against myocardial reperfusion injury. Study on cardiac function. Chin Med J 1992; 105: 11-17
- 9 Xu X, Zhang S, Zhang L et al. The neuroprotection of puerarin against cerebral ischemia is associated with the prevention of apoptosis in rats. Planta Med 2005; 71: 585-591
- 10 Xiong FL, Sun XH, Gan L et al. Puerarin protects rat pancreatic islets from damage by hydrogen peroxide. Eur J Pharmacol 2006; 529: 1-7
- 11 Dong LP, Wang TY. Effects of puerarin against glutamate excitotoxicity on cultured mouse cerebral cortical neurons. Zhongguo Yao Li Xue Bao 1998; 19: 339-342
- 12 Cos P, De Bruyne T, Apers S et al. Phytoestrogens: recent developments. Planta Med 2003; 69: 589-599
- 13 Boué SM, Wiese TE, Nehls S et al. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem 2003; 51: 2193-2199
- 14 Green PS, Simpkins JW. Neuroprotective effects of estrogens: potential mechanisms of action. Int J Dev Neurosci 2000; 18: 347-358
- 15 Amantea D, Russo R, Bagetta G et al. From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens. Pharmacol Res 2005; 52: 119-132
- 16 Asthana S, Baker LD, Tate PS. Role of estrogen in the treatment and prevention of Alzheimer’s disease. Expert Opin Investig Drugs 1997; 6: 1203-1209
- 17 Chen J, Backus KH, Deitmer JW. Intracellular calcium transients and potassium current oscillations evoked by glutamate in cultured rat astrocytes. J Neurosci 1997; 17: 7278-7287
- 18 Mattson MP, Goodman Y. Different amyloidogenic peptides share a similar mechanism of neurotoxicity involving reactive oxygen species and calcium. Brain Res 1995; 676: 219-224
- 19 Mills GC. The purification and properties of glutathione peroxidase of erythrocytes. J Biol Chem 1959; 234: 502-506
- 20 Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 1952; 195: 133-140
- 21 Henderson VW. Hormone therapy and Alzheimer’s disease: benefit or harm?. Expert Opin Pharmacother 2004; 5: 389-406
- 22 Quintanilla RA, Muñoz FJ, Metcalfe MJ et al. Trolox and 17beta-estradiol protect against amyloid beta-peptide neurotoxicity by a mechanism that involves modulation of the Wnt signaling pathway. J Biol Chem 2005; 280: 11615-11625
- 23 Nilsen J, Chen S, Irwin RW et al. Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function. BMC Neurosci 2006; 7: 74
- 24 Benlhabib E, Baker JI, Keyler DE et al. Composition, red blood cell uptake, and serum protein binding of phytoestrogens extracted from commercial kudzu-root and soy preparations. J Med Food 2002; 5: 109-123
- 25 Zhang Y, Chen J, Zhang C et al. Analysis of the estrogenic components in kudzu root by bioassay and high performance liquid chromatography. J Steroid Biochem Mol Biol 2005; 94: 375-381
- 26 Filipcik P, Cente M, Ferencik M et al. The role of oxidative stress in the pathogenesis of Alzheimer’s disease. Bratisl Lek Listy 2006; 107: 384-394
- 27 Yatin SM, Varadarajan S, Link CD et al. In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid beta-peptide (1-42). Neurobiol Aging 1999; 20: 325-330
- 28 Goodman Y, Bruce AJ, Cheng B et al. Estrogens attenuate and corticosterone exacerbates excitotoxicity, oxidative injury, and amyloid beta-peptide toxicity in hippocampal neurons. J Neurochem 1996; 66: 1836-1844
- 29 Jiang B, Liu JH, Bao YM et al. Hydrogen peroxide-induced apoptosis in pc12 cells and the protective effect of puerarin. Cell Biol Int 2003; 27: 1025-1031
- 30 Plattner F, Angelo M, Giese KP. The roles of cyclin-dependent kinase 5 and glycogen synthase kinase 3 in tau hyperphosphorylation. J Biol Chem 2006; 281: 25457-25465
- 31 Cross DA, Alessi DR, Cohen P et al. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995; 378: 785-789
- 32 Hernández F, Borrell J, Guaza C et al. Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J Neurochem 2002; 83: 1529-1533
- 33 Goodenough S, Schleusner D, Pietrzik C et al. Glycogen synthase kinase 3beta links neuroprotection by 17beta-estradiol to key Alzheimer processes. Neuroscience 2005; 132: 581-589
- 34 Vaidya RJ, Ray RM, ohnson LR. Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1. Cell Mol Life Sci 2006; 63: 2871-2879
- 35 Suhara T, Magrané J, Rosen K et al. Abeta42 generation is toxic to endothelial cells and inhibits eNOS function through an Akt/GSK-3beta signaling-dependent mechanism. Neurobiol Aging 2003; 24: 437-451
- 36 Magrané J, Rosen KM, Smith RC et al. Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J Neurosci 2005; 25: 10960-10969
- 37 Wang P, Henning SM, Heber D. Limitations of MTT and MTS-based assays for measurement of antiproliferative activity of green tea polyphenols. PLoS One 2010; 5: e10202
- 38 Gomes A, Fernandes E, Lima JL. Fluorescence probes used for detection of reactive oxygen species. J Biochem Biophys Methods 2005; 65: 45-80