Walnut (Juglans regia) Peptides Reverse Sleep Deprivation-Induced Memory Impairment in Rat via Alleviating Oxidative Stress

The aim of this study was to determine the neuroprotective effects of walnut protein hydrolysates (WPH) against memory deficits induced by sleep deprivation (SD) in rat and further to identify and characterize the potent neuroprotective peptides against glutamate-induced apoptosis in PC12 cells. Results showed that a remarkable amelioration effect on behavioral performance in Morris water maze test was observed for WPH and its low molecular weight fraction WPHL, especially for WPHL. Additionally, a reduction of antioxidant defense (catalase, glutathione peroxidase (GSH-px), and superoxide dismutase (SOD)) and an increase of malondialdehyde content induced by SD were normalized in brain of rat after oral administration of WPH and WPHL. Then three neuroprotective peptides including GGW, VYY, and LLPF were identified from WPHL, which could protect PC12 cells against glutamate-induced apoptosis with relative cell viability of 78.29 ± 3.09%, 80.65 ± 1.74%, and 83.97 ± 3.06%, respectively, versus glutamate group 48.61 ± 3.99%. The possible mechanism underlying their protective effects of GGW and VYY could be related to their strong radical scavenging activity as well as their ability to reduce reactive oxygen species production and the depletion of SOD and GSH-px in PC12 cells. Notably, the marked neuroprotective effects of LLPF, which did not show obvious free-radical scavenging activity in vitro, could be attributed to its strong effects on inhibiting Ca2+ influx and mitochondrial membrane potential collapse. Additionally, all these peptides could regulate the expression of apoptosis-related proteins (Bax and Bcl-2). Therefore, walnut peptides might be regarded as the potential nutraceuticals against neurodegenerative disorders associated with memory deficits.