Inhibition of Amylin Fibril Formation and Protection of Islet Β-cells by Medicinal Plants

Misfolding of some proteins, their self-assembly into insoluble amyloid structures underlies many diseases, constituting a group of amyloid-related pathology. Fibrillation of peptide hormone of pancreas, amylin, is considered as one of the causes of death of β-cells in type 2 diabetes. In this work we studied in vitro protection of islet β-cells from death in the presence of aggregated amylin by ethanol extracts of rose petals (Rosa damascena), melilot (Melilotus officinalis), leaves of grape (Vitis vinifera), sorrel (Rumex Confertus) and blackberry (Rubus Caesius), and by eleven fractions, isolated from these plants (coumarin, phenol glycoside, flavonoid and anthracene derivative). A rather low IC50 values in protection of βcells were estimated for the extracts (0.03-1.5 μg/ml) and their fractions (0.04-3.9 μg/ml). The inhibition of amylin aggregation by several plant extracts and fractions in vitro was studied using ThT fluorescence method. The IC50 values in deceleration of the peptide aggregation were between 1.76-7.24 μg/ml. A strong correlation (r = 0.99, p=0.0005) was observed between IC50 values in protection of β-cells and amylin aggregation. Probably, both of these processes are conditioned by prevention of amylin aggregation and/or decomposition of its preformed aggregates by plant preparations. These results allow recommending frequent use of effective plants by persons at risk group, and considering these plants as sources for antidiabetic agents. INTRODUCTION: Misfolding and self-assembly into insoluble amyloid fibrillar structure of the protein underlies many diseases that make up the group of amyloid-related diseases. Currently, there are not yet found therapeutic agents successfully preventing the formation of fibrillar aggregates, suitable for treatment of amyloid-dependent diseases. Therefore, natural compounds with a broad spectrum of biological activities are considered as sources for developing the new therapeutics 1-4 . QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.IJP.2(5).234-41 Article can be accessed online on: www.ijpjournal.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.IJP.2(5).234-41 Amylin is a secretory product of pancreatic β-cells 5, 6 . It is a regulatory peptide functioning in the islet β-cells, where it participates in regulation of glucose metabolism along with insulin. Amyloid deposits of amylin were found in the islets of βcells in type 2 diabetes in humans and some mammals. Aggregated amylin is cytotoxic and is one of the causes of β-cell loss in type 2 diabetes mellitus 7 . There is a lot of information concerning the inhibition of amyloidosis of amylin by natural compounds as flavonoids (myricetin, quercetin, kaempferol, etc.), polyphenols (curcumin, epigallocatechin gallate, rosmarinic acid, etc.) and others 8-11 . It is believed, the cytotoxicity of the peptide on βcells can be reduced by these compounds. Indeed, epigallocatechin gallate in green tea in vitro inhibited amylin amyloidogenesis and destabilized its preformed aggregates 10 . The polyphenols