Alleviative and Anti-Inflammatory effects of tuna blood hydrolysates on MPP plus and TNF- α- induced Parkinson-Like disease model through the regulation of Keap1-Nrf2 antioxidant pathway and apoptosis

The pathophysiology of Parkinson ' s disease (PD) is linked to oxidative stress and inflammatory-induced cell death of dopaminergic neurons in substantia nigra pars compacta (SNpc). The current study aims to investigate the effects of tuna blood hydrolysate (TBH) on the neurodegeneration of Parkinson-like disease models using neurotoxin-induced SH-SY5Y cells differentiated to be dopaminergic-like neurons. It was found that TBH at concentrations ranging from 5 to 250 mu g/ml can reduce differentiated SH-SY5Y cell death after exposure to 1methyl-4-phenylpyridinium (MPP + ) co-treated with TBH for 24 h. Real -time PCR results indicated that TBH enhanced the expressions of NAD(P)H quinone dehydrogenase 1 ( NQO1 ), catalase ( CAT ), and thioredoxin reductase ( TrxR1 ), which are Nrf2 downstream antioxidant genes. Bioinformatic analysis and molecular docking revealed that the peptide found in TBH, IPGQPGLPGPPGPPGPPGLG, could penetrate the cell and blood - brain barrier and strongly bind the Keap1-Kelch domain, causing Nrf2 nuclear translocation. Consequently, the upregulation of antioxidant genes ameliorates ROS and reduces dopaminergic neuron death. Another, TBH can reduce differentiated SH-SY5Y cell death and intracellular ROS after exposure to 24 h of co-treatment between TBH and tumor necrosis factor-alpha (TNF- alpha). Western blot analysis was performed to investigate apoptosisrelated proteins. Bcl2 and BDNF are dramatically increased, while BAX, cytochrome c , caspase3, caspase9, and cleaved caspase9 are significantly decreased in co-treating differentiated SH-SY5Y cells with TBH and TNF- alpha. These findings demonstrated that TBH can suppress the apoptosis of inflammatory differentiated SH-SY5Y cells. Taken together, this study suggests that TBH can alleviate neurodegeneration and has anti-inflammatory effects on dopaminergic-like neurons in the simulation of a PD condition.