Polysaccharide from Pycnoporus sanguineus ameliorates dextran sulfate sodium‐induced colitis via helper T cells repertoire modulation and autophagy suppression

Abstract

Inflammatory bowel disease (IBD) is a chronic autoimmune disease associated with various risk factors. Pycnoporus sanguineus (L.) Murrill is a saprotrophic fungus used worldwide for its industrial and medical purposes. Here, polysaccharide from P. sanguineus (PPS) was explored for its antiinflammatory potential in a murine colitis model of IBD induced by dextran sulfate sodium (DSS). PPS ameliorated the colitis as manifested by the lowered disease activity index (DAI), prolonged colon, and reduced serum lipopolysaccharide (LPS). PPS recovered the histological lesion by upregulating the expressions of Zonula occludens-1 (ZO-1), E-cadherin, and proliferating cell nuclear antigen (PCNA). PPS inhibited the helper T cells (Th)-mediated immune response by decreasing the proportions of Th cells (including Th2 cells, Th17 cells, and regulatory T cells), which was accompanied with reductions on myeloperoxidase (MPO) activity and releases of several interleukins and chemokines within the colon. Moreover, PPS exhibited an evident inhibition on autophagy, in which the ratio of light chain 3 (LC3) II/I was declined, while the expression of p62 and Beclin-1 was increased. The present study highlighted important clinical implications for the treatment application of PPS against IBD, which relies on the regulation of Th cells repertoire and autophagy suppression to restore epithelium barrier.

SETD8 involved in the progression of inflammatory bowel disease via epigenetically regulating p62 expression

“…Although our previous results suggested that SETD8 plays an important role in inflammatory process, the underlying mechanism remains unclear. In consistent with some previous studies, 22,23 using a public dataset of UC and CD patients, we identified that p62 was upregulated in IBD patients, and our western blot analysis confirmed the result (Fig. 5a,b).…”

“…21 In particular, some studies reported that elevated protein level of p62 was observed in the colon mucosa of ulcerative colitis (UC) patients and DSS-induced colitis mice, accompanied with upregulated inflammatory cytokines. 22,23 Collectively, these observations suggested a pivotal role of p62 in inflammatory diseases.…”

Natural-Derived Polysaccharides From Plants, Mushrooms, and Seaweeds for the Treatment of Inflammatory Bowel Disease

“…P. sanguineus is a saprophytic fungus, which is widely applied in industry and medicine all over the world. Li M. X. et al (2020) extracted a polysaccharide PPS from P. sanguineus and found that PPS could alleviate the colitis induced by DSS, which is manifested by reducing DAI, colon shortening, colonic MPO activity, and serum LPS concentration. PPS could effectively restored intestinal barrier function by increasing the expression of ZO-1, E-cadherin, and PCNA.…”

Exosomes derived from T regulatory cells relieve inflammatory bowel disease by transferring miR‐195a‐3p

“…As a scaffold protein, ZO‐1 can connect claudins, occludin, and cytoskeletal fibrin to form a stable tight junction complex. ZO‐1 protein expression is reduced in IBD, 21 suggesting impaired intestinal mucosal barrier function in IBD. TNF‐α, a key mediator of intestinal inflammation, has been shown to increase intestinal epithelial tight junction permeability 22 and induce apoptosis and inflammatory response in intestinal epithelial cells 23 .…”