title: Beneficial Effect of Astragaloside on Alzheimer's Disease Condition Using Cultured Primary Cortical Cells Under β-amyloid Exposure.
abstract: β-amyloid (Aβ)-mediated neuronal apoptosis contributes to the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether astragalosides (AST) could inhibit Aβ-induced apoptosis in vivo and in vitro and to explore the underlying mechanisms. Amyloid β-protein fragment 25-35 (Aβ25-35) was administered to cerebral lateral ventricle of rats to make the AD models in vivo. AST was able to attenuate both cortical cell degeneration and memory deficits in the AD rats. AST also inhibited Aβ25-35-induced cytotoxicity (e.g., decreased cell viability); apoptosis (e.g., increased caspase-3 expression, increased DNA fragmentation, and Tau hyperphosphorylation); synaptotoxicity (e.g., increased loss of both a dendritic marker, microtubule-associated protein 2 (MAP-2) and synaptic proteins, synaptophysins); and mitochondrial dysfunction (e.g., increased mitochondrial membrane potential) in cultured primary rat cortical cells. The beneficial effect of AST in reducing Aβ-induced cytotoxicity, apoptosis, and mitochondrial dysfunction in cortical cells were blocked by inhibition of phosphoinositide 3-kinase (PI3K)-dependent protein kinase B (PKB, as known as AKT) activation with LY294002. In addition, inhibition of extracellular protein kinase (ERK) with U0126 shared with the AST the same beneficial effects in reducing Aβ-induced apoptosis. Our data suggest that the cortical PI3K/AKT and MAPK (or ERK) pathways as appealing therapeutic targets in treating AD, and AST may have a positive impact on AD treatment via modulation of both PI3K/AKT and ERK pathways.
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan.|The Ph.D. Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, 110, Taiwan.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Emergency Medicine, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Hung-Jung
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Emergency Medicine, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Chien-Chin
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Surgery, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Bor-Chih
authors.initials: BC
authors.lastname: Cheng
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Liu
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Medical Research, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, 821, Taiwan.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Hsu
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan.|Department of Emergency Medicine, Chi Mei Medical Center, Tainan, 710, Taiwan.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, 710, Taiwan. gaujang@mail2000.com.tw.|Department of Neurology, Chi Mei Medical Center, Tainan, 710, Taiwan. gaujang@mail2000.com.tw.
authors.forename: Kao-Chang
authors.initials: KC
authors.lastname: Lin
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002070:Butadienes; D009570:Nitriles; D012503:Saponins; C113580:U 0126; D016875:tau Proteins; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3
keywords: Amyloid beta (Aβ); Astragalosides; Memory dysfunction; Neuronal degeneration; Synaptotoxicity