Baicalein, a typical flavonoid compound, has neuroprotective properties in several neurological disorders. Autophagy plays a central role in maintaining the cellular homeostasis, and is involved in the pathogenesis of Parkinson's disease (PD). Recently, baicalein has been reported to induce autophagy. Therefore, the current study was designed to investigate whether baicalein could protect against rotenone-induced neurotoxicity via induction of autophagy both in SH-SY5Y cells and in a mouse model. A chronic PD mouse model was established by continuous intragastric administration of rotenone for 12 weeks. Baicalein was administrated from 7 to 12 week. Our results showed that baicalein prevented rotenone-induced behavioral deficits, dopaminergic neuronal loss, apoptosis and mitochondrial dysfunction. Furthermore, baicalein restored rotenone-impaired autophagy, and blocking the baicalein-induced autophagy using 3-methyladenine inhibited the neuroprotective effects of bacalein. Baicalein increased cell viability and restored mitochondrial function in SH-SY5Y cells. The beneficial effect of baicalein was abrogated by 3-methyladenine treatment. Furthermore, rapamycin increased autopahgy and reduced the rotenone-induced neurotoxicity in SH-SY5Y cells. Collectively, these results suggest that baicalein could prevent rotenone-induced neurotoxicity via restoring autophagy.
Key words baicalein; neuroprotection; Parkinson's disease; autophagyParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, and postural instability.1-3) The main pathological characteristic of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, the loss of dopamine in the striatum, and the presence of intracytoplasmic inclusions in surviving neurons known as Lewy bodies.4) Several biochemical mechanisms related to the pathogenesis of PD include oxidative stress, mitochondrial dysfunction, protein aggregation and misfolding, apoptosis, excitotoxicity, and neuroinflammation.5,6) Currently, none of therapies has been convincingly shown to slow down or prevent the progression of PD, and additional effective treatments for this disease are urgently needed.Baicalein, a flavonoid, is derived from the root of the traditional Chinese herb Scutellariabaicalensis GEORGI. Baicalein has been reported to have neuroprotective effects in PD model through anti-inflammatory, anti-apoptosis, and anti-oxidative actions. In vitro, baicalein protected PC12 cells against 6-hydroxydopamine (6-OHDA)-or rotenone-induced neurotoxicity, 7,8) and ameliorated the 6-OHDA-induced SH-SY5Y cell apoptosis.9) In vivo, baicalein exerted neuroprotective effects in 6-OHDA-induced neurotoxicity in rats 9) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice.10) However, the exact mechanism of baicalein is poorly understood.Autophagy is a highly conservative cellular process by which cells degrade and recycle of bulk cytosolic proteins and dama...