No abstract

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. M2 macrophages possess certain anti-inflammation activity. Accordingly, the current study set out to investigate the potential mechanism of M2 macrophage-derived extracellular vesicles (M2-EVs) in UC inflammation. Firstly, mouse peritoneal macrophages were induced to M2 phenotype, and M2-EVs were isolated. , the murine model of UC was established, and the length and weight of the colon, disease activity index (DAI), apoptosis, and inflammatory response of UC mice were measured. Young adult mouse colon (YAMC) cells were induced with the help of lipopolysaccharide. LncRNA maternally expressed 3 (LncRNA MEG3), miR-20b-5p, and cAMP responsive element binding protein 1 (CREB1) expression patterns were detected in UC models. In addition, we analyzed the binding relationship among MEG3, miR-20b-5p, and CREB1. UC mice presented with shortened colon length, lightened weight, increased DAI score, enhanced apoptosis, and significant inflammatory cell infiltration, while M2-EVs reversed these trends. In vitro , M2-EVs increased UC cell viability and reduced inflammation. Mechanistic experimentation revealed that M2-EVs transferred MEG3 into YAMC cells to up-regulate MEG3 expression and promote CREB1 transcription by competitively binding to miR-20b-5p. Moreover, up-regulation of MEG3 in M2-EVs enhanced the protective effect of M2-EVs on UC cells, while over-expression of miR-20b-5p attenuated the aforementioned protective effect of M2-EVs on UC mice and cells. Collectively, our findings revealed that M2-EVs carrying MEG3 enhanced UC cell viability and reduced inflammatory responses via the miR-20b-5p/CREB1 axis, thus alleviating UC inflammation.

Pectic polysaccharides extracted from Rauvolfia verticillata (Lour.)Baill.var. hainanensis Tsiang exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.

This study was to investigate the effects and mechanisms of pectic polysaccharides (PP) extracted from Rauvolfia verticillata (Lour.) Baill. var. hainanensis Tsiang on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC). Eighty female BALB/c mice were randomly divided into four groups: Control, DSS, DSS + salicylazosulfapyridine (SASP), and DSS+ PP. The disease activity index (DAI), overall physical activity, and blood stool were monitored daily to evaluate severity of UC. Histological scores of the colon were observed. The expression of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways in colon tissues and bone marrow-derived dendritic cells (DCs) was assessed by western blot, immunohistochemistry, electrophoretic mobility shift assay (EMSA) and real time polymerase chain reaction (RT-PCR). Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The overall physical activity, DAI and histological scores decreased in DSS+SASP and DSS+PP groups, compared with the DSS-alone group. Also, tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) reduced significantly while the expression of IκBα was up-regulated, extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 were activated, in DSS+SASP and DSS+PP groups. PP inhibited activation of MAPKs and NF-κB pathways in the bone-marrow-derived DCs. In conclusion, PP significantly ameliorated murine DSS-induced UC model, via regulation of MAPKs and NF-κB pathways in DCs.