Cork polyphenols, an alternative strategy against amyloid-beta fibrillization

Alzheimer disease (AD) is a genetic-based neurodegenerative disorder characterized by progressive impairment in memory. Aging is the primary cause behind the increase in the prevalence of neurodegenerative disorders (where neural cells suffer functional or sensory loss). The hallmark of AD is the presence of amyloid beta peptide in senile plaques and the presence of neurofibrillary tangles. [1] Natural polyphenols with pyrogallol and galloyl groups present in several natural tea catechins, has been referred as effective against peptide aggregation and as a promisimg protector of neuronal loss in AD patients [2].

Based on these knowledge, we extracted and purified natural polyphenols from cork (e.g. castalagin and vescalagin) and we tested them for their antioxidant activity (AO) and capacity to inhibit amyloid-beta fibrillization. We found that the isolated polyphenols present a AO similar to other natural polyphenols (e.g. EGCG) and are able to inhibit the aggregation/fibrillization of amyloid-beta. [3]

Our results confirm that cork polyphenols, such as, castalagin and vescalagin, while presenting AO in vitro, are also able to rescue the metabolic activity of SH-SY5Y human neuroblastoma cells in the presence of Abeta42. These polyphenols also inhibit amyloid-beta fibrillization, as shown in aggregation assays monitored by circular dichroism, fluorescence spectroscopy, electron microscopy and atomic force microscope. We observed a concentration-dependent decay of Abeta42 fluorescence that paralleled a significant aggregation decrease monitored by electron microscopy and atomic force microscopy. Most importantly, castalagin and vescalagin rescued SH-SY5Y cells from Abeta42-induced cytotoxicity, favoring higher cell viability than epigallocatechin gallate (EGCG). Based on its powerful antioxidant and anti-fibrillization properties we suggest these polyphenols might used as part of a treatment strategy for AD.

Acknowledgements: Authors acknowledge the financial support from Projeto “NORTE-08-5369-FSE-000037”, financed by Programa Operacional Norte 2020. This work was also supported by the European Union H2020, grant numbers H2020-TWINN-2015-692333 – CHEM2NATURE and H2020-WIDESPREAD-2014-2-668983 – FORECAST.

References:

1.Porat, Y., A. Abramowitz, and E. Gazit, Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem Biol Drug Des, 2006. 67(1): p. 27-37.

2.Mecocci, P. and M.C. Polidori, Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2012. 1822(5): p. 631-638.

3.Kim, H.-S., M.J. Quon, and J.-a. Kim, New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biology, 2014. 2: p. 187-195.