H. Ramshini; N. Kovsari; A. Moghaddasi
Abstract
Amyloid aggregate plaques are the hallmarks of many neurodegenerative disorders including Alzheimer’s disease. Thus, reducing amyloid deposits is an attractive approach to improve the therapeutic arsenal for the diseases. Despite of intensive research carried out, there is no therapeutic agent ...
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Amyloid aggregate plaques are the hallmarks of many neurodegenerative disorders including Alzheimer’s disease. Thus, reducing amyloid deposits is an attractive approach to improve the therapeutic arsenal for the diseases. Despite of intensive research carried out, there is no therapeutic agent directed towards inhibition of aggregation formation. One important approach in the development of therapeutics is the use of herbal extracts, which are rich in aromatic small molecules. This study aimed to explore the inhibitory activity of Satureia hortensis extract against the fibril formation of hen egg-white lysozyme. In this experimental study, amyloid fibrillation was formed in hen egg-white lysozyme under acidic conditions at high temperature. Lysozyme (2 mg/mL) was dissolved in glycine buffer 50 mM, pH=2.5 and incubated at 57°C for the specified durations, while being gently stirred. Various techniques including thioflavin T, ANS fluorescence assay, and atomic force microscopy were used to confirm fibrillation. Data were analyzed through SPSS 16 using descriptive statistics as well as independent t-test.In the absence of Satureia hortensis, mature amyloid aggregates became evident after 48 hours of incubation but upon incubation with various extract concentrations (ranging from 0.25 to 1 mg/ml), formation of amyloid fibrils and oligomers was inhibited. The inhibition was dose-dependent and the best concentration was 1 mg/ml. Our results showed that, the extract was effective in all of amyloid formation processes including lag, polymerization, and equilibrium phases. Also, cytotoxicity of oligomers in the presence of the extract significantly (P<0.05) decreased, as indicated by the MTT assay. Based on inhibitory role of the extract on cytotoxicity of amyloid fibers and its inhibitory effect on all processes of amyloid aggregation, it could be used as a novel inhibitor for Alzheimer's disease.
