Neuroprotection of round scad (Decapterus maruadsi) hydrolysate in glutamate-damaged PC12 cells: Possible involved signaling pathways and potential bioactive peptides

Neuroprotective effects of round scad hydrolysate (RSH) on neurotoxicity induced by glutamate in PC12 cells and the involved signaling pathways were explored in this study. In addition, the potential bioactive peptides in RSH were separated and identified by UPLC-QTOF-MS/MS. Results showed that pretreatment with RSH at 0.1-1.0 mg/mL could dose-dependently enhance cell viability, alleviate mitochondrial dysfunction and inhibit apoptosis in glutamate-damaged PC12 cells, indicating that RSH could exert neuroprotection against glutamate neurotoxicity. Several signaling pathways including Bax/Bcl-2-related apoptotic pathway, Nrf2-mediated oxidative stress response pathway and CREB-related neuronal survival pathway were involved in the neuroprotection. Furthermore, 23 peptides with potential neuroprotection were identified, and Tyr- and Trp-containing peptides might be potent contributors to the neuroprotection. Molecular docking studies indicated that these peptides such as PPW might directly bind to Keap1 to modulate nuclear factor-E2-related factor (Nrf2) pathway. Thus, RSH can be used as a potential neuroprotective ingredient for preventing neurodegenerative diseases.