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Neuroprotection and neuronal recovery under the oxidative stress achieved by enhanced lipid membrane interaction with flavonoids

Flavonoids, polyphenolic biomolecules with antioxidative activity, have recently emerged as potential novel therapeutics for neurodegenerative diseases. The research of the flavonoids and their use for diagnostic and therapeutic purposes have created a need for understanding the complex interactions of cells with flavonoids, particularly neuroprotective ones like myricetin (aglycone) and myricitrin (glycoside). Membrane-flavonoid interactions are of crucial importance for both the cell uptake and toxicological investigations. The presence of flavonoids embedded within a lipid bilayer, can lead to changes in lipid packing by modifying interactions amongst the lipid headgroups and/or acyl tails. Therefore, investigation of flavonoids interaction with lipid membranes using IR spectroscopy, microcalorimetry, atomic force microscopy (AFM) and force spectroscopy (FS) have been undertaken. Model membranes consisting of a lipid mixture of unsaturated phosphatidylcholine, sphinogomyelin and cholesterol (PC/SM/Chol) and P19 neurons were chosen enabling investigation of not only the nanomechanical properties of the neuronal membranes and their interactions with different molecular species, but also testing of flavonoid ability to inhibit lipid peroxidation and lipid structural reorganization in model membranes and neurons under oxidative stress in vitro. Our research deciphered interactions of neuroprotective flavonoids, myricetin and myricitrin with model neuronal membranes and neuronal cells through their delicate response at physiological and oxidative stress environment. Obtained results pointed that the time needed to complete the oxidative reaction might be considered as the measure of flavonoid protective power. The nanomechanics (elasticity), surface topography (roughness) of model lipid membranes and P19 neurons as well as the thermodynamic and kinetic data that result from the oxidative damage are quantified for the first time showing specific effects on the elasticity of the supported lipid bilayers and neuronal cells at both physiological and oxidative stress conditions. Functionality of the flavonoids has been related to the organization and elasticity of the model neuronal membranes and neuronal cells.

lipid peroxidation ; flavonoids ; model lipid membrane ; neuronal cells

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