Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

“…In addition, existing fibrils of α-Syn are disaggregated by baicalein (Zhu et al, 2004). Subsequent biophysical studies and in vitro/vivo studies demonstrated that baicalein is capable of mitigating α-Syn aggregation and reducing cytotoxicity (Caruana et al, 2012;Hu et al, 2016;Jiang et al, 2010;Lu et al, 2011). Baicalein is a potent inhibitor of α-Syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-Syn fibrillation in cell-free systems.…”

Targeting α-Synuclein for PD Therapeutics: A Pursuit on All Fronts

“…Baicalein in combination with β-cyclodextrin synergistically inhibited α-syn aggregation and disaggregated preformed fibrils even at very low concentrations [365]. Two studies also reported the in vivo protective effects of Baicalein on decreasing α-syn aggregation [392,393]. Baicalein prevented the transition from α-syn monomers to oligomers, associated with behavioral improvement and neuroprotection in the striatum of rotenone-induced PD in rats [392].…”

“…Two studies also reported the in vivo protective effects of Baicalein on decreasing α-syn aggregation [392,393]. Baicalein prevented the transition from α-syn monomers to oligomers, associated with behavioral improvement and neuroprotection in the striatum of rotenone-induced PD in rats [392]. Furthermore, Baicalein attenuated MPTP-induced α-syn aggregate formation in the injected SN of mice [393].…”

Therapeutic Potential of Baicalein in Parkinson’s Disease: Focus on Inhibition of α-Synuclein Oligomerization and Aggregation

“…• Inhibits α-syn aggregation [81] of α-syn oligomers was observed in the thoracic spinal cord, midbrain, and ileum. In the light of this, baicalein could be able to prevent the PD progression through inhibiting the aggregation and formation of α-syn oligomers [61]. Although, the exact molecular mechanism of baicalein through which inhibition of aggregation of α-syn proteins takes place is yet to be elucidated, but characteristic molecular structure-based mechanism of baicalein has been proposed.…”