The Study Of The Treatment Effects Of Lentinan On Inflammatory Bowel Disease And Colitis-associated Cancer

Inflammatory bowel disease(IBD), including ulcerative colitis(UC) and Crohn's disease(CD), is a chronic non-specific colitis inflammatory disorder. The pathogenesis of IBD is unclear, but evidence showed that the occurrence of IBD was related to immune system disorders, genetic and environment factors. IBD constitutes a significant health burden to millions of people and its incidence is increasing rapidly. Besides, UC is more likely to develop into colorectal cancer. However, effects of drugs for the treatment of IBD at present are not satisfactory and most of the drugs have serious side effects, so there is a demand for the discovery of novel and effective drugs with low side effects.Lentinan, extracted from the mycelium of Lentinus Edodes, is a kind of fungal polysaccharide with immunoregulatory activity. Based on its immunomodulatory effect, lentinan is extensively used for chronic viral hepatitis and advanced malignant tumors in clinic, which makes it become a potential drug for IBD treatment.In this study, according to the two main forms of IBD, we established three animal models, including acute UC induced by high dose of dextran sodium sulfate(DSS), chronic UC induced by low dose of DSS and CD induced by TNBS. Results showed that lentinan significantly improved body weight loss, diarrhea, shortened colon length, and histological scores of the above-mentioned three models. In addition, lentinan significantly attenuated the tumorigenesis in azoxymethane(AOM)/DSS induced colitis-associated cancer(CAC) through inhibiting the inflammation-cancer transformation.In vitro, calcium assay showed that lentinan inhibited the calcium signals mediated by TLR4. Dual luciferase reporter gene assay and Western blot showed lentinan inhibited the NF-?B activiation, and nuclear translocation of NF-?B was also inhibited as can be seen in immunofluorescence and immunohistochemistry. The detection of cytokine antibody arrays showed that lentinan significantly decreased the expression level of kinds of inflammatory cytokines, together with a decreased expression of colon cancer markers showed in the immunohistochemical staining of CAC mice.These results suggest that lentinan exhibits intestinal anti-inflammatory activity through inhibition of inflammatory cytokines expression associated with the inhibition of calcium signals and NF-?B pathway related to TLR4, which provide potential new treatments for IBD and CAC.