Related Signal Pathways Effects Of Milk-derived CGMP On IBD

Casein glycomacropeptide(CGMP)is a resource of bioactive protein derived from bovine κ-caseino and lack of aromatic amino acids,which application is in diets for phenylketonuria patients.CGMP has been proved to have many bioactivities,which has nutritional identity,as well as improving intelligence,promoting probiotics and immune regulatory.The two major clinically defined forms of inflammatory bowel disease(IBD),crohn’s disease(CD)and ulcerative colitis(UC),are chronic remittent or progressive inflammatory disease.Now most of scholars claimed that the intestines mucosa immune dysregulation,deficiency of intestines mucosa barrier,genetic and environmental factors may affect the entire gastrointestinal tract involved in the occurrence of IBD.The drug treatment for IBD includes 5-aminosalicylic acid,corticosteroids and immune inhibitor in clinic,but the effect is not satisfactory and toxic.At present the research focus on develop the more effective nutrition therapy in this field.The discovery that CGMP may participate in intestinal mucosal immune response,and regulate the balance of immune cell subsets,which has the potential to be a new way of relieve and treat for IBD.Therefore,further research the molecular mechanism of CGMP on IBD has important practical significance.The ulcerative colitis(UC)mouse model was established by oxazolone-induction.CGMP(50 or 500 mg/kg bw·d)and sulfasalazine(SASP,40 mg/kg bw·d)was intragastically administrated into mice for four consecutive days.The morphological and histological damages of colon in UC mice were examined by HE staining and the protein levels of CD4 、 CD8 、 MAdCAM-1 、 sIgA in colon tissues were evaluated by immunohistochemistry.And then western blotting was used to detect the expression difference of MAPK MEKK1 and TGF-β1/Smads Smad3、Smad7,in order to explore the mechnasim of bovine casein glycomacropeptide affecting mice with ulcerative colitis.The results showed that CGMP alleviated oxazolone-induced body weight loss as well as morphological and histological damages,and attenuated the expression of MAdCAM-1、 CD4、CD8 and promoted the expression of sIgA in colon tissue,and that CGMP inhibited the expression of MKEE1 and Smad7 through mediating the MAPK pathway and TGF-β1/Smads.Thus,CMMP indirectly inhibited the phosphorylation of IκB as well as activated IκBα and inhibited the activation of NF-κB.Accordingly,CGMP could maintain the balance of intestinal mucosal immunity and protect the intestinal mucosal immune barrier function,in order to alleviate inflammation and effectively improve ulcerative colitis.Therefore,this study provided a scientific basis for the anti-inflammatory molecular mechanism and the stability of intestinal mucosal internal environment maintained by CGMP.CGMP as a functional material can be used in the biological immune therapy of ulcerative colitis.