title: Protective effect of Puerarin on β-amyloid-induced neurotoxicity in rat hippocampal neurons.
abstract: Puerarin (CAS Number 3681-99-0), a major isoflavone glycoside purified from Pueraria lobata, was reported to possess 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.
authors.affiliation: Beijing Institute of Technology, Beijing, People's Republic of China. franklinbit@163.com
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.forename: B
authors.initials: B
authors.lastname: Xie
authors.forename: F
authors.initials: F
authors.lastname: Cai
authors.forename: G
authors.initials: G
authors.lastname: Wu
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006690:Bisbenzimidazole; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D007529:Isoflavones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D002374:Catalase; D005979:Glutathione Peroxidase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051058:Oncogene Protein v-akt; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D006690:Bisbenzimidazole; C033607:puerarin