Silymarin-Based Nanosheets Efficiently Protect Mitochondria against Oxidative Damage Mediated by α-Synuclein Amyloid Aggregates

An increasing body of evidence suggests that mitochondrial dysfunction mediated by α-synuclein (α-syn) aggregates plays a key role in the pathogenesis of Parkinson's disease (PD), leading to intensive research for the discovery and development of compounds with mitoprotective effects. Silymarin (SIL) is a complex mixture of flavonolignans with a wide range of protective effects on mitochondria under stress conditions. Herein, the potency of SIL, in bulk and nano forms, in protecting mitochondria against oxidative damage induced by α-syn aggregates has been investigated. Mitochondria were isolated from rat brain and liver tissues as well as human neuroblastoma SH-SY5Y cells, and damage was evaluated by using a range of biochemical assays. The obtained results show a substantial difference in the response of various mitochondria to oxidative damage induced by α-syn aggregates, with brain mitochondria exhibiting the highest vulnerability. We found that incubation of mitochondria with either bulk or nano forms of SIL before exposure to α-syn aggregates significantly attenuated oxidative damage in a dose-dependent manner. In parallel, α-syn aggregates aged in the presence of bulk or nano forms of SIL considerably lost their capacity to cause mitochondrial damage. While both bulk and nano forms of SIL showed significant mitoprotective effects, SIL nanosheets were much more effective. Possible mechanisms relating to the mitoprotective effects of SIL and the higher efficacy of SIL nanosheets are discussed. The obtained results suggest natural polyphenol-based nanoparticles as an efficient therapeutic approach in relation to amyloid-related diseases, such as PD.