Screening Of Anti-Intestinal In Flammatory Peptides Derived From Preserved Egg White And Study Of Their Anti-Inflammatory Mechnism

Inflammatory bowel disease is a chronic and recurrent inflammatory disease that occurs in the intestine.Traditional drug therapy can relieve clinical symptoms,but the clinical symptoms cannot be completely controlled,while there are some side effects.Egg-derived bioactive components are one of the recent research hotspots in the field of food science.The anti-bacterial,anti-viral,anti-hypertensive,anti-oxidative,anti-inflammatory and immunoregulatory activities of egg components have been confirmed.The development and application of egg-derived bioactive components is expected to provide new therapeutic strategies for inflammatory bowel disease.Our previous studies have shown that SGD-PEW has the effect of alleviating the inflammatory process of DSS-induced mouse colitis,and inhibiting TNF-?-induced IL-8secretion and inflammatory cytokine gene expression in Caco-2 cells.However,there are few studies on its anti-inflammatory material basis and the anti-inflammatory mechanism of SGD-PEW.Therefore,we investigated the anti-inflammatory material basis of SGD-PEW and then further explored its anti-inflammatory mechanism,in order to provide a theoretical reference for a new anti-intestinal inflammatory dietary strategy based on peptides derived from preserved egg white.First,the anti-inflammatory effect of the peptides derived from SGD-PEW was evaluated using an in vitro inflammatory model of TNF-?-induced Caco-2 cells.The results showed that peptides derived from preserved egg white DEDTQAMPFR(DR-10),DEDTQAMPF(DF-9),MLGATSL(ML-7)and MSYSAGF(MF-7)significantly down-regulated IL-8 secretion at a concentration of 0.25 mg/mL.In addition,these four peptides significantly inhibited the gene expression of pro-inflammatory cytokines including TNF-?,IL-8,IL-6,IL-1? and IL-12 and promoted the gene expression of anti-inflammatory cytokines of IL-10 in TNF-?-induced Caco-2 cells.At the same time,DR-10,DF-9,ML-7 and MF-7 significantly inhibited the phosphorylation of JNK,while DR-10 and DF-9 significantly decreased the phosphorylation levels of I?B and p38.These results indicated that ML-7 and MF-7 exerted their anti-inflammatory activity through the MAPK signaling pathway.Whereas,DR-10 and DF-9 inhibited the TNF-?-induced activation of NF-?B and MAPK signaling pathways in Caco-2 cells.Further,the anti-inflammatory effects of DR-10,ML-7,SR-7 and MF-7 in vivo were determined by a mouse model of dextran sodium sulfate(DSS)-induced colitis.The results showed that DR-10,ML-7,SR-7 and MF-7 significantly ameliorated the clinical symptoms of DSS-induced mice colitis,such as the weight loss,disease activity index increasing,the colon shortening,spleen hypertrophy and histological scores increasing.In the DSS-induced mouse colitis model,administration of DR-10,ML-7,SR-7 and MF-7 also significantly inhibited the local secretion of pro-inflammatory cytokines TNF-? and IL-6,and markedly down-regulatedgene expression of pro-inflammatory cytokines,including TNF-?,IL-6,IL-17,IL-1?,IFN-? and MCP-1.Overall,MF-7showed the best effect of alleviating DSS-induced colitis among four peptides.Taken together,the peptides derived from preserved egg white MF-7?DR-10?ML-7and SR-7 have good inhibitory effects on inflammation both in vitro and in vivo.Therefore,the peptides derived from preserved egg white MF-7?DR-10?ML-7 and SR-7have good anti-inflammatory biological activity.The results indicated that MF-7,DR-10,ML-7 and SR-7 may be potential promising candidates for the treatment of IBD.