Walnut (Juglans regia L.) glutelin-derived peptides as novel candidates for cognitive enhancement: targeting oxidative stress and neuroinflammation

Walnut protein hydrolysates exert neuroprotection. This study further evaluated hydrolysates from walnut albumin, globulin, prolamin, glutelin by alkaline, neutral protease, and trypsin by detecting radical-scavenging and anti-oxidant/inflammatory activities in lipopolysaccharide-stimulated BV2 microglia. Further, novel memory-enhancing bioactive peptides were identified by in-silico experiments and cell validation. Among hydrolysates, alkaline protease-derived glutelin hydrolysates (WAGluP) exhibited strongest bioactivity, showing higher radical-scavenging capacity, increased the activities of superoxide-dismutase (SOD) and glutathione-peroxidase (GSH-PX) by 19.961 and 4.359 U/mg prot, and reduced nitric-oxide (NO, −13.129 μmol/g prot) production. Moreover, WAGluP decreased tumor-necrosis-factor-α (TNF-α, −21.2 %) and interleukin-6 (IL-6, −12.3 %) levels. Additionally, LWPF, WLPF, and YFPF were identified as potential memory-enhancing candidates by peptidomic, PeptideRanker, and molecular docking from WAGluP, in which LWPF and WLPF increased SOD activity by 71.9 and 54.01 %, and GSH-PX activity by 87.32 and 99.12 %. Overall, WAGluP and its peptides exert multitarget antioxidant and anti-inflammatory effects with memory-enhancing potential, supporting walnut-glutelin-peptides for neuroprotective functional-foods. • Walnut glutelin peptides by alkaline protease (WAGluP) show best redox activity. • WAGluP optimally regulate LPS-induced memory impairment in BV2 cells. • WAGluP rich in anti-inflammatory, antioxidant, neuroprotective amino acid. • Novel memory-improving peptides LWPF, WLPF, YFPF were identified from WAGluP.