Abstract
Deposition of proteins is a key pathogenic feature of more than 20 amyloid-related diseases. Inhibiting or reversing amyloid aggregation via the use of small molecules is proposed as two useful approaches in hampering the development of these diseases. In this research, we examined the inhibitory and disruptive effects of apigenin, a common dietary flavonoid with multiple pharmacological properties, against human insulin fibrillization. Besides, we investigated the potential cytotoxicity of insulin fibrils on SK-N-MC cells in the presence and absence of apigenin. The increase in Thioflavin T (ThT) and anilinonaphthalene-8-sulfonic acid (ANS) fluorescent intensities and Congo red absorbance were inhibited by simultaneous incubation of various concentrations of apigenin with insulin, in a dose-dependent manner. The spectroscopy results were confirmed by transmission electron microscopy, where lower extent of fibrillar structures was observed in the presence of apigenin. In addition, the cell exposure to the co-incubated insulin amyloids with apigenin led to the increased viability and decreased LDH release dose-dependently, compared to cells exposed to insulin fibrils alone. Co-incubation with apigenin also attenuated the extent of apoptotic cell death induced by insulin fibrils. It can be concluded that apigenin possess in vitro anti-amyloidogenic activities as well as protective effects against insulin amyloids cytotoxicity.
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