Abstract Title:

Beneficial Effect of Astragaloside on Alzheimer's Disease Condition Using Cultured Primary Cortical Cells Underβ-amyloid Exposure.

Abstract Source:

Mol Neurobiol. 2016 Dec ;53(10):7329-7340. Epub 2015 Dec 22. PMID: 26696494

Abstract Author(s):

Ching-Ping Chang, Yu-Fan Liu, Hung-Jung Lin, Chien-Chin Hsu, Bor-Chih Cheng, Wen-Pin Liu, Mao-Tsun Lin, Shu-Fen Hsu, Li-Sheng Chang, Kao-Chang Lin

Article Affiliation:

Ching-Ping Chang


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., increasedcaspase-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 membranepotential) 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) activationwith 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 ASTmay have a positive impact on AD treatment via modulation of both PI3K/AKT and ERK pathways.

Study Type : In Vitro Study

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