Drug Screening to Amyloid Beta from Selaginella Tamariscina
|School||Central South University|
|Keywords||Alzheimer’s disease β-amyloid drug screening Selainellatamariscina|
Abstract:One of the key features of Alzheimer’s disease is amyloid beta-protein (AP) aggregated and sedimentated into insoluble fiber in extracelluar, and grown into senile plaques (SP). These fibers induce nerve fiber tangles (NFT) and neuronal loss. The main symptomses are memories persistent recession, activity disorder and cognitive decline. Therefore, treating A(3as targets, many efforts have been made on the development of effective inhibitors to prevent Aβ fibril formation or disassemble the formed A(3fibrils and inhibit the nerve toxicities of Aβ and to find effective way to prevent and control AD.In this study, we take nine drugs as potential inhibitors, which extracted from traditional Chinses medcies (TCM) Selaginella tamariscina. The inhibitory properties of these extract drugs on A(3were evaluated by AFM analysis and confirmed by ThT fluorescence assay. Our results demonstrated that three of them could play a positive role on Aβ, that D1#, D3#and D8#can significantly inhibit the aggregation of Aβ. Through AFM images, we could find little oligemers or nonfinalized matters. And these three drugs can strongly decrease the ThT fluorescence which suggests that they can reduce the β-sheet structures.Futher more, we take MTT cell toxicity experiment, circular dichroism (CD) and ThT fluorescence assay to take a depth research on these picked three screening drugs. Our results showed that D1#, D3#and D8#can not only inhibit Aβ(1-42) fibrillogenesis, but can disaggregated preformed Aβfibers by testing through ThT fluorescence assay. CD test results futher confirmed the three drugs have strong binding force, like π-π conjugation and hydrogen bonding with Aβ which have a huge impact on the secondary structures of Aβ. Moreover, the toxicity of Aβ aggregates significantly inhibited in the presence of D3#or D8#as expected.Through a series ways of screening analysis, two kinds of filtered selaginella genus ingredients exhibit a strong inhibitory effect on Aβ(1-42) and have excellent nerve cell protection against Aβ(1-42), and are expected as potential drug candidateds for AD treatment.In this essay, there are29figures,4tables and115references.