The present study aimed to investigate the combined effects of defatted walnut meal hydrolysate (DWMH) and tea polyphenols (TP) on learning improvement and to explain mechanistically why the combined treatments were more effective than either subject alone. In the step-down avoidance test and the Morris water maze test, codelivery of DWMH and TP was more effective than either individual supplement in reversing memory impairment in scopolamine-treated mice. Mixing with TP significantly facilitated the protective effects of DWMH or DWMH-derived peptides (cationic peptide P1 and anionic peptide P2) on H2O2-injured SH-SY5Y cells. Although combination treatment with TP and DWMH did not significantly alter systemic exposure to P1 or P2 in rats, it significantly increased the accumulation of the two peptides in the mouse brain. In addition, TP significantly improved cellular uptake of P1 and P2 by brain capillary endothelial cells, indicating that TP enhanced the blood-brain barrier permeation of DWMH-derived peptides. The proposed explanation for the advantage of combined treatment with TP and DWMH in reversing memory impairment was that TP enhanced both the protective effects of DWMH on nerve cells and the accumulation of DWMH in the brain. Our study can aid efforts to develop products and investigate the effects of nutrient combinations on brain disorders.
Keywords: blood−brain barrier penetration; combination; defatted walnut meal hydrolysate; neuroprotective effect; tea polyphenols.