Study On Molecular Mechanism Of Isoflavone Aglycone Curing AD And Inhibiting Aβ Eurotoxicity

Objective:In this paper, the purpose is to investigate the prevention effect of isoflavone aglycone (IA) on the Alzheimer's disease (AD), and to explore its molecular mechanism of neuroprotection by inhibiting of Aβneurotoxicity. Method:The preparation technology of extracting IA from defatted soybean powder was optimized. The PC 12 cell impaired model induced by H2O2 and A(3 and SAM-P/8 mice model was built successfully. Mouse performance in learning and memory were then evaluated by Y-maze. The oxidationresistance of PC 12 cell and SAM-P/8 mice was measured by determination of serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities,the concentration of malondialdehyde (MDA). In addition, the P-secretase activity of the hippocampus tissue was monitored by fluorometry to determine the formation of Aβ. Changes of the hippocampal neurons were observed under a light microscope. The cortex acetylcholinesterase (AchE) activity was monitored to determine the reduction of Ach. The signal pathway of IA's inhibition effect on the neurotoxicity of Aβwas investigated on the result of the determination of the regulation effect of IA and Myr antagonist on PKC activity,α,β-secretase activity. Result:High purity isoflavone aglycone (content 70.98%)was extrated from defatted soybean powder by the optimized preparation technology. IA can significantly improve the learning and memory ability,oxidationresistance of AD mice. IA can cause the up-regulation of a secretase activity and down regulation ofβ-secretase activity, So that IA can reduce the information of Aβand thereby effectively protect the nervous system. Conclusion:The prevention effect of IA on AD was investigated at the cell level and animal level. IA can regulate the a,β-secretase activity by activate the PKC signaling pathway, and then inhibit the information of Aβ. The molecular mechanism that how IA effectively protect the nervous system is made clear.The result of this investigation can provide scientific basis for IA to be used in AD treatment.