Walnut peptide WEKPPVSH in alleviating oxidative stress and inflammation in lipopolysaccharide-activated BV-2 microglia via the Nrf2/HO-1 and NF-κB/p38 MAPK pathways.

The peptide WEKPPVSH from walnut protein hydrolyzate was used to evaluate the antioxidant and anti-inflammatory protective effect on lipopolysaccharide (LPS)-activated BV-2 microglia and its possible mechanism. The results indicated that WEKPPVSH significantly decreased nitric oxide (NO) and reactive oxygen species (ROS) generation in a dose-dependent manner, and significantly up-regulated superoxide dismutase and catalase activities (P < 0.01). Results of enzyme-linked immunosorbent assay (ELISA) showed that WEKPPVSH significantly mitigated the secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) (P < 0.01). Immunofluorescence analysis exhibited that WEKPPVSH down-regulated p65 translocation to the cell nucleus. Western blotting showed that WEKPPVSH up-regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1), and down-regulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p-IκB/IκB, p-p65/p65 and p-p38/p38. In summary, WEKPPVSH might protect against oxidative stress and inflammation in LPS-stimulated BV-2 microglia by enhancing the Nrf2/HO-1 signaling pathway and blocking the nuclear factor-κB/p38 mitogen - activated protein kinase (NF-κB/p38 MAPK) signaling pathway. The results provided an experimental basis for the research and development of walnut peptide products.