Wheat peptides inhibit the activation of MAPK and NF-κB inflammatory pathways and maintain epithelial barrier integrity in NSAID-induced intestinal epithelial injury.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has negative effects on the gastrointestinal tract, but the proton pump inhibitors currently in use only protect against gastrointestinal disease and may even make NSAID-induced enteropathy worse. Therefore, new approaches to treating enteropathy are required. This study aimed to investigate the protective effect of wheat peptides (WPs) against NSAID-induced intestinal damage in mice and their mechanism. Here, an in vivo mouse model was built to investigate the protective and reparative effects of different concentrations of WPs on NSAID-induced intestinal injury. WPs ameliorated NSAID-induced weight loss and small intestinal tissue damage in mice. WP treatment inhibited NSAID-induced injury leading to increased levels of oxidative stress and expression levels of inflammatory factors. WPs protected and repaired the integrity and permeability injury of the intestinal tight junction induced by NSAIDs. An in vitro Caco-2 cell model was built with lipopolysaccharide (LPS). WP pretreatment inhibited LPS-induced changes in the Caco-2 cell permeability and elevated the levels of oxidative stress. WPs inhibited LPS-induced phosphorylation of NF-κB p65 and mitogen-activated protein kinase (MAPK) signaling pathways and reduced the expression of inflammatory factors. In addition, WPs increased tight junction protein expression, which contributed to improved intestinal epithelial dysfunction. Our results suggest that WPs can ameliorate NSAID-induced impairment of intestinal barrier functional integrity by improving intestinal oxidative stress levels and reducing inflammatory factor expression through inhibition of NF-κB p65 and MAPK signaling pathway activation. WPs can therefore be used as potential dietary supplements to reduce NSAID-induced injury of the intestine.

Pea-derived peptides, VLP, LLP, VA, and LL, improve insulin resistance in HepG2 cells via activating IRS-1/PI3K/AKT and blocking ROS-mediated p38MAPK signaling.

This study evaluated the effect of four peptides, VLP, LLP, LL, and LL from pea on regulating glucose metabolism and antioxidant through IRS-1/PI3K/AKT and p38MAPK signal pathway in IR-HepG2 cell induced by 10-6 M insulin. The genes expression of PEPCK, G6Pase, GLUT2, and IRS-1 and proteins of IRS-1, p(Ser307)-IRS-1, AKT, p(Ser473)-AKT, p38MAPK, and p-p38MAPK were determined by RT-PCR and western blotting, respectively. Results show that they displayed highly potent on stimulation glucose metabolism and relief oxidative stress in IR-HepG2 cells. VLP, LLP, VA, and LL reduced Ser307 phosphorylation of IRS-1 and promoted Ser473 phosphorylation of AKT. Among them, LLP, VA, and LL increased the expression both gene and protein of GLUT2, and VLP and LL reduced p38MAPK phosphorylation showing strong antioxidant capacity. Therefore, pea oligopeptides have considerable potential for reversing the metabolic abnormalities associated with type 2 diabetes. PRACTICAL APPLICATIONS: This paper examined the intervention effect of VLP, LLP, VA, and LL that from pea on insulin resistance, and the mechanisms were detected by western blotting. The results provide a theoretical knowledge for the prevention of insulin resistance in T2D of pea-derived peptides and lay the foundation for the development of functional products and drugs in the future.