Dendrobium Officinale Polysaccharides Improve Irritable Bowel Syndrome And Colitis-associated Cancer By Activating Nrf2 Pathway

Irritable bowel syndrome(IBS)is a common functional gastrointestinal disease with diarrhea-type IBS accounting for the largest proportion of IBS cases.So far,the etiology of IBS is still unclear.Some studies have shown that oxidative stress and Low-grade inflammation may take part in the pathogenesis of IBS.The persistent nourishment of oxidative stress and chronic inflammation in patients with chronic inflammatory bowel disease induces malignant progression of the disease into colitis-associated colon cancer(CAC),a common and high-mortality cancer.Since oxidative stress is a key issue in establishing the links between inflammation-cancer early in cancer,increasing the bodv’s antioxidant capacity is the primary step in cutting off the inflammatory-cancer cycle.Activating the expression of Keapl/Nrf2 pathway and its downstream target protein are essential for the body to protect against oxidative stress and inflammatory damage.Previous studies have confirmed that Dendrobium Officinale polysaccharides(DOPS)has good antioxidant and anti-inflammatory properties.Therefore,based on the above research,in this paper,we proposes a scientific hypothesis that Dendrobium Officinale polysaccharides can improve irritable bowel syndrome and colitis-associated colon cancer by activating Keapl/Nrf2 pathway.we study the therapeutic effect and mechanism of Dendrobium Officinale polysaccharides and provide experimental evidence.ObjectiveTo preliminary evaluate whether Dendrobium Officinale polysaccharides has a efficacy in protecting against irritable bowel syndrome and colitis-associated colon in mice,and assess the impact of Dendrobium Officinale polysaccharides on Keapl/Nrf2 pathway,including Nrf2,HO-1,Keap1 as well as the activation and infiltration of neutrophils.Methods1.Effect of DOPS on treating irritable bowel syndromeIirritable bowel syndrom was induced in male KM mice by tail-clamp stress,and then were randomly grouped into normal group,model group and DOPS-administered group(100 mg/Kg).Detection index:body weight,fecal water content,spleen and t.hymus coefficient,peripheral blood leukocytes,lymphocytes,monocytes,macrophage content,serum SOD,MDA,IL-1α,IL-1 β,IL-6,IL-10,TNF-α content,colon histopathological section.2.Mechanism of DOPS on treating irritable bowel syndromeThe expression of the Keapl/Nrf2-related protein and the activation of neutrophils in the colon tissues of the above groups were examined.3.Effect of DOPS on treating colitis-associated colon cancerColitis-associated colon cancer model was established by 2%DSS combined with AOM for three cycle.After the first cycle of modeling,the model group animals were divided into:AOM/DSS model group and DOPS administration group(100mg/Kg).Detection indicators:body weight,colon macroscopic score,colon tumor condition,spleen and thymus coefficient,peripheral blood leukocytes,lymphocytes,monocytes,macrophage content,serum SOD,MDA,IL-1α,IL-1β,IL-6,IL-10,TNF-α content,pathological sections of colon tissue.4.Mechanism of DOPS on treating colitis-associated colon cancerThe expression of the Keapl/Nrf2-related protein and the activation of neutrophils in the colon tumor tissues of the above groups were examined.Results1.Effect of DOPS on treating irritable bowel syndromeThe serum levels of MDA,IL-1α,IL-1 β,IL-6 and TNF-α in the model group were observably increased,and the SOD content was dramatically decreased{P<0.05 or P<0.01),After administration of DOPS,serum MDA,IL-1α,IL-1β,IL-6 and TNF-α were markedly decreased,and SOD content was observably increased(P<0.05 or P<0.01).2.Mechanism of DOPS on treating irritable bowel syndromeThe expression of Nrf2 and HO-1 in the colon of model group was significantly decreased(P<0.05or P<0.01).The expression of Nrf2 and HO-1 was significantly increased after the administration of DOPS(P<0.05 or P<0.01)3.Effect of DOPS on treating colitis-associated colon cancerThe serum level of MDA,IL-1α,IL-1 β,IL-6 and TNF-α in AOM/DSS model group were dramatically increased,SOD content was markedly decreased(P<0.05 or P<0.01);After DOPS administered,the content of MDA,IL-1α,IL-1β,IL-6 and TNF-α in serum were observably decreased,and SOD content was memorably increased(P<0.05 or P<0.01).4.Mechanism of DOPS on treating colitis-associated colon cancerThe expression of Nrf2 and H0-1 in colon and colon tumors of AOM/DSS model group was significantly decreased(P<0.05 or P<0.01).The expression of Nrf2 and HO-1 was significantly increased after DOPS administration(P<0.05 or P<0.01).ConclusionDendrobium Officinale polysaccharides has therapeutic effects on irritable bowel syndrome and colitis-associated colon cancer,and its mechanism was achieved by activating the Keapl/Nrf2 pathway-mediated antioxidant stress pathway,improving the body’s antioxidant capacity and reducing inflammatory cell infiltration.