Neuroprotective and Memory-Enhancing Effects of Antioxidant Peptide From Walnut ( <i>Juglans regia</i> L.) Protein Hydrolysates

Abstract

Peptides have been reported to possess interesting biological properties. The present study was designed to evaluate neuroprotective and memory-enhancing effects of antioxidant peptide from walnut ( Juglans regia L.) protein hydrolysates. The neuroprotective effect of walnut peptide (WP) against oxidative stress on PC12 cells was evaluated. And zebrafish was used as the model to corroborate the effect. Its effect on learning and memory of mice using the Morris water maze and the step-down passive avoidance tests were performed. Moreover, the acute toxicity of WP was carried out to assess its safety profile. It was found that WP was able to suppress H 2 O 2 -induced cell death in PC12 cells. In the zebrafish model, WP had an obvious neuroprotective effect, and the ratio reached 42% at 222 µg/mL. The mechanism study revealed that WP could inhibit the activity of caspases 3/7 and 8, reduce the mRNA expression levels of Bax and glial cell line-derived neurotrophic factor, and improve the mRNA expression level of brain-derived neurotrophic factor significantly. Besides, the treatment of mice with WP shortened the escape latency and exhibited much longer target time and more crossing times significantly, compared with untreated control groups in the Morris water maze test. Similarly, the step-down passive avoidance test showed that WP could ameliorate memory impairments. The administrated dose (20.1 g/kg body weight [BW]) did not produce mortality or treatment-related adverse effects with regard to BW, general behavior, or relative organ weights of the tested male and female mice. The current results indicated that WP could exert neuroprotective effect, and attenuated learning and memory impairments. These ameliorating effects of WP may be useful for treatment of memory impairment in Alzheimer’s and its related diseases.