Silybin as a potent inhibitor of a-synuclein aggregation and associated cytotoxicity against neuroblastoma cells induced by zinc oxide nanoparticles

a-synuclein (a-syn) amyloid fibrils, the leading neurotoxic types, are predominately formed through interaction with nanoparticles (NPs). However, some natural compounds like silybin can reduce the formation of NPs-induced amyloid fibrils and related cytotoxicity. Herein, we assayed the ZnO-induced a-syn amyloid fibril formation and underlying cytotoxicity in the absence and presence of silybin using a wide range of multispectroscopic (ThT fluorescence, Congo red absorbance, and CD), TEM, and cellular (MTT, LDH, ROS, and caspase-3) approaches. Spectroscopy data and TEM investigation showed that ZnO NPs accelerate the induction of a-syn amyloid fibrils in the amyloidogenic conditions. However, silybin as a bioactive compound can result in inhibition of a-syn fibrillogenesis induced by ZnO NPs. The potent inhibitory impact of silybin on cytotoxicity of a-syn amyloid fibrils induced by ZnO NPs was also assessed by cellular assays. It was depicted that the mortality, LDH release, ROS production, and caspase-3 activity upon addition of silybin were less than those reported in absence of this small molecule. These outcomes revealed that silybin is of great importance as neuroprotective and therapeutic small molecules for NP-induced protein aggregation and related cytotoxicity.