Ameliorative Effect Of An Acid Polysaccharide From Phellinus Linteus On DSS-induced Ulcerative Colitis Mice

Phellinus linteus is a rare medicinal fungus.Polysaccharides,the main biological components of which have strong anti-tumor and anti-inflammatory activities,have attracted much attention in Asia for centuries.This study focused on the improvement of Phellinus linteus acid polysaccharide(PLAP)on mice models of ulcerative colitis(UC)induced by sodium dextran sulfate(DSS)and its related mechanism.PLAP was purified from solid-state fermentation mycelia and administered in UC mice at the dosages of 300 and 600 mg/kg for 17 d.During the experimental period,body weight loss,food intake,disease activity index(DAI),and morphological analysis of colon tissues in all mice were recorded;the serum levels of cytokines(TNF-α,IL-1β,IL-6,IL-10),myeloperoxidase(MPO),and inducible nitric oxide synthase(i NOS)were measured by Enzyme-linked immunosorbent assay(ELISA).Levels of tight-junction proteins(ZO-1,Claudin-1,Occludin)and m RNA involved in inflammatory signaling pathways were determined by q PCR.Gut microbiota was analyzed by high-throughput sequencing and the concentration of short-chain fatty acids(SCFAs)in colonic content was detected by GC.UC symptoms such as body weight loss,reduced food intake,increased DAI,and colonic damage were relieved by PLAP.PLAP significantly decreased the levels of proinflammatory factors such as TNF-α,IL-6 and IL-1β,increased the level of IL-10 of antiinflammatory factors,and decreased the levels of oxidative stress-related enzymes i NOS and MPO(P<0.05 or P<0.01).q PCR analysis showed that PLAP significantly downregulated p65 and p38 phosphorylation and TLR-4 m RNA transcription level(P <0.05 or P < 0.01).Treatment of PLAP resulted in enhanced expression of ZO-1,Occludin,and Claudin-1.The results of high-throughput sequencing revealed that the diversity and species abundance of gut microbiota in UC mice were significantly restored by PLAP(P<0.05 or P< 0.01).At the genus level,PLAP significantly increased the relative abundance of beneficial bacteria such as Lactobacillus 、 norank＿f＿Muribaculaceae 、Bifidobacterium 、 Akkermansia 、 Faecalibaculum 、 Romboutsia 、 Alistipes 、norank＿f＿norank＿o＿Clostridia＿UCG-014 、 Odoribacter and Parasutterella,decreased the relative abundance of harmful bacteria such as Enterococcus and Turicibacter.GC analysis showed that PLAP displayed a beneficial effect of increasing SCFAs.To sum up,PLAP significantly alleviates the symptoms of UC mice based on the reduction of inflammation and oxidative stress levels,modulation of gut microbiota composition and restoration of intestinal barrier function,and has potential for development and application.