Curcumin alleviates experimental colitis via a potential mechanism involving memory B cells and Bcl-6-Syk-BLNK signaling.

BACKGROUND: Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease (IBD), which is mainly related to lymphocytes (T or B cells, incl-uding memory B cells), mast cells, activated neutrophils, and macrophages. As the precursor of B cells, the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells, whose dysfunction can easily lead to autoimmune diseases, including IBD. AIM: To investigate whether or not curcumin (Cur) can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling. METHODS: Colitis was induced in mice with a dextran sulphate sodium (DSS) solution in drinking water. Colitis mice were given Cur (100 mg/kg/d) orally for 14 con-secutive days. The colonic weight, colonic length, intestinal weight index, occult blood scores, and histological scores of mice were examined to evaluate the curative effect. The levels of memory B cells in peripheral blood of mice were measured by flow cytometry, and IL-1ß, IL-6, IL-10, IL-7A, and TNF-α expression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay. Western blot was used to measure the expression of Bcl-6, BLNK, Syk, and other signaling pathway related proteins. RESULTS: After Cur treatment for 14 d, the body weight, colonic weight, colonic length, colonic weight index, and colonic pathological injury of mice with colitis were ameliorated. The secretion of IL-1ß, IL-6, TNF-α, and IL-7A was statistically decreased, while the IL-35 and IL-10 levels were considerably increased. Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM, IgG, IgA, FCRL5, CD103, FasL, PD-1, CD38, and CXCR3 on the surface of CD19+ CD27+ B cells, while the number of CD19+ CD27+ IL-10+ and CD19+ CD27+ Tim-3+ B cells increased significantly. In addition, Cur significantly inhibited the protein levels of Syk, p-Syk, Bcl-6, and CIN85, and increased BLNK and p-BLNK expression in colitis mice. CONCLUSION: Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.

Chimonanthus nitens Oliv. Leaf Granule Ameliorates DSS-Induced Acute Colitis Through Treg Cell Improvement, Oxidative Stress Reduction, and Gut Microflora Modulation.

The rising incidence of ulcerative colitis has become a new challenge for public health. Chimonanthus nitens Oliv. leaf granule (COG) is a natural medicine used for the treatment of respiratory diseases, which has excellent anti-inflammatory and antioxidant effects. However, the therapeutic effect of COG in ulcerative colitis (UC) has not been reported. Here, the experimental colitis was treated with dextran sodium sulfate (DSS) and COG. After treatment with high (30 g/kg), medium (15 g/kg), and low (7.5 g/kg) doses of COG for 11 consecutive days, the body weight, disease activity index (DAI) score, colon length, colon weight index, and the pathological score of mice were effectively improved. COG significantly reduced the levels of inflammatory cytokines in UC mice in vitro and in vivo and restored the secretion levels of IL-6 and IL-10 in the colon. Meanwhile, compared to mice with colitis, COG-treated mice showed lower levels of MDA, MPO, NO, and eNOS and higher levels of GSH-Px and MAO, which indicated that oxidative stress damage in colitic mice was alleviated by COG. Moreover, less Th17 and more Tregs were observed in the COG-treated groups. In addition, COG improved the diversity and relative abundance of gut microflora in the colon of colitic mice, and Lachnospiraceae_NK4A136_group and Lachnospiraceae_UCG-006 were obviously regulated at the genus level. In summary, COG has a protective effect on DSS-induced experimental colitis, mainly through inhibition of immune-inflammatory responses and oxidative stress and regulation of mTreg cell responses and intestinal flora composition.

Curcumin regulates the homeostasis of Th17/Treg and improves the composition of gut microbiota in type 2 diabetic mice with colitis.

Diabetes mellitus (DM) is one of the most common complications in patients with ulcerative colitis (UC). Curcumin has a wide range of bioactive and pharmacological properties and is commonly used as an adjunct to the treatment of UC and DM. However, the role of curcumin in UC complicated by DM has not been elucidated. Therefore, this study was conducted to construct a model of UC complicating diabetes by inducing UC in DB mice (spontaneously diabetic) with dextran sodium sulfate. In this study, curcumin (100 mg/kg/day) significantly improved the symptoms of diabetes complicated by UC, with a lower insulin level, heavier weight, longer and lighter colons, fewer mucosal ulcers and less inflammatory cell infiltration. Moreover, compared to untreated DB mice with colitis, curcumin-treated mice showed weaker Th17 responses and stronger Treg responses. In addition, curcumin regulated the diversity and relative abundance of intestinal microbiota in mice with UC complicated by DM at the phylum, class, order, family and genus levels. Collectively, curcumin effectively alleviated colitis in mice with type 2 diabetes mellitus by restoring the homeostasis of Th17/Treg and improving the composition of the intestinal microbiota.