Natural polyphenols from cork as an alternative strategy against amyloid-beta fibrilization

Natural polyphenols, are a group of compounds referred as promising drugs against oxidative stress and protein aggregation in several diseases. [1] Apart from environmental or genetic factors, oxidative stress lead to free radical attack on cells and contributes significantly to increase, for example, neuron loss. Therefore, the relationship between the antioxidant capacity of natural compounds and their activity towards these neurodegenerative disorders became a case of study, namely, in their capacity to inhibit protein aggregation. [2] 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 protein in senile plaques and the presence of neurofibrillary tangles. [3] Natural polyphenols has been referred as effective against peptide aggregation and as a promisimg protector of neuronal loss in AD patients [4]. In this context, we isolated phenols from the outer bark of Quercus suber L. and studied their cytoprotective and antioxidant behaviour [5]. Our results confirm that polyphenols, such as, castalagin and vescalagin, display antioxidant activity in vitro and rescue the metabolic activity of SH-SY5Y human neuroblastoma cells in the presence of Abeta42. These polyphenols also inhibit amyloid-beta fibrillation, as shown in aggregation assays with circular dichroism, 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. 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 antifibrillogenic properties we suggest these polyphenols might be beneficial for the treatment of AD.

REFERENCES

1.             Ramassamy, C., Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: A review of their intracellular targets. European Journal of Pharmacology, 2006. 545(1): p. 51-64.

2.             Butterfield, D.A. and J. Kanski, Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mechanisms of Ageing and Development, 2001. 122(9): p. 945-962.

3.             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.

4.             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.

5.             Araujo, A.R., et al., Cork extracts reduce UV-mediated DNA fragmentation and cell death. Rsc Advances, 2015. 5(116): p. 96151-96157.