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PLoS One ; 10(11): e0141708, 2015.
Article in English | MEDLINE | ID: mdl-26536106

ABSTRACT

Inhibition of ß-amyloid (Aß) aggregation in the cerebral cortex of the brain is a promising therapeutic and defensive strategy in identification of disease modifying agents for Alzheimer's disease (AD). Since natural products are considered as the current alternative trend for the discovery of AD drugs, the present study aims at the evaluation of anti-amyloidogenic potential of the marine seaweed Padina gymnospora. Prevention of aggregation and disaggregation of the mature fibril formation of Aß 25-35 by acetone extracts of P. gymnospora (ACTPG) was evaluated in two phases by Thioflavin T assay. The results were further confirmed by confocal laser scanning microscopy (CLSM) analysis and Fourier transform infrared (FTIR) spectroscopic analysis. The results of antiaggregation and disaggregation assay showed that the increase in fluorescence intensity of aggregated Aß and the co-treatment of ACTPG (250 µg/ml) with Aß 25-35, an extensive decrease in the fluorescence intensity was observed in both phases, which suggests that ACTPG prevents the oligomers formation and disaggregation of mature fibrils. In addition, ACTPG was subjected to column chromatography and the bioactivity was screened based on the cholinesterase inhibitory activity. Finally, the active fraction was subjected to LC-MS/MS analysis for the identification of bioactive compounds. Overall, the results suggest that the bioactive compound alpha bisabolol present in the alga might be responsible for the observed cholinesterase inhibition with the IC50 value < 10 µg/ml for both AChE and BuChE when compared to standard drug donepezil (IC50 value < 6 µg/ml) and support its use for the treatment of neurological disorders.


Subject(s)
Amyloid beta-Peptides/metabolism , Cholinesterase Inhibitors/metabolism , Peptide Fragments/metabolism , Plant Extracts/metabolism , Seaweed/metabolism , Acetone/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/chemistry , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Chromatography, High Pressure Liquid , Donepezil , Humans , Indans/chemistry , Indans/metabolism , Microscopy, Confocal , Peptide Fragments/chemistry , Piperidines/chemistry , Piperidines/metabolism , Plant Extracts/chemistry , Protein Binding , Protein Structure, Secondary , Seaweed/chemistry , Spectroscopy, Fourier Transform Infrared , Tandem Mass Spectrometry
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