Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway

Abstract

Curcumin (Cur) is a natural active phenolic compound extracted from the root of Curcuma Longa L. It has anti‐inflammatory, anti‐tumor and other pharmacological activities, and is commonly used to treat ulcerative colitis (UC). However, it is not clear whether curcumin regulates the function and differentiation of Breg cells to treat UC. In this study, mice with chronic colitis were induced by dextran sulfate sodium (DSS), and treated with curcumin for 12 days. Curcumin effectively improved the body weight, colonic weight, colonic length, decreased colonic weight index and pathological injury score under colonoscopy in mice with chronic colitis, and significantly inhibited the production of IL‐1β, IL‐6, IL‐33, CCL‐2, IFN‐γ, TNF‐α, and promoted the secretion of IL‐4, IL‐10, IL‐13 and IgA. Importantly, curcumin markedly upregulated CD3−CD19+CD1d+, CD3−CD19+CD25+, CD3−CD19+Foxp3+Breg cells level and significantly down‐regulated CD3−CD19+PD‐L1+, CD3−CD19+tim‐1+, CD3−CD19+ CD27+ Breg cells level. In addition, our results also showed that curcumin observably inhibited TLR2, TLR4, TLR5, MyD88, IRAK4, p‐IRAK4, NF‐κB P65, IRAK1, TRAF6, TAB1, TAB2, TAK1, MKK3, MKK6, p38MAPK, p‐p38MAPK and CREB expression in TLR/MyD88 signaling pathway. These results suggest that curcumin can regulate the differentiation and function of Breg cell to alleviate DSS‐induced colitis, which may be realized by inhibiting TLR/MyD88 pathway.

Protective effect of five-flavor sophora flavescens enteric-coated capsules on inflammatory bowel disease and its molecular mechanism

“…TNF-α, IL-6, TLR4, IL-17, NF-kB, TRIF, and IFN-γ are all important inflammatory factors and have some clinical significance for the diagnosis of UC (Du & Ha, 2020). Related studies have showed that disturbance of the internal environment (such as disturbed gut microbiota) can induce the increased expression of TLR4 on epithelial cells, endothelial cells and other membranes in intestinal mucosa, and combine with MyD88 to form TLR-MyD88 complex, so as to activate related signaling kinases, leading to the activation of transcription factor NF-κB, releasing NF-κB and translocating to the nucleus (Huang et al, 2023). When the number of NF-κB entering the nucleus increases, NF-κB entering the nucleus binds to DNA, thereby initiating a series of gene transcription, enhancing transcription, and promoting more inflammatory factors (such as TNF-α, IL-6, IL-17, TRIF, IFN-γ and so on), and then the phenomenon of chemokine secretion and macrophage infiltration occurs, ultimately forming a "cytokine storm" effect, aggravating the inflammatory response, mediating intestinal damage (such as ulcers, necrosis and), even causing carcinogenesis because of long-term accumulation (Xue et al, 2017).…”

Traditional Chinese medicine treats ulcerative colitis by regulating gut microbiota, signaling pathway and cytokine: Future novel method option for pharmacotherapy

“…Curcumin is the main effective ingredient of Curcuma longa L. in the treatment of UC [ 111 ]. It mainly exerts its therapeutic effect on UC by regulating signaling pathways, such as TLR/MyD88, MAPK, and PI3K/AKT, and inhibiting pro-inflammatory cytokines, such as IL-1β, TNF-α, IL-33, CCL-2, IL-6, and TGF-β1 [ 112 ]. Curcumin has been found to increase the killing power of pathogenic gram-positive and gram-negative bacteria while promoting the production of short-chain fatty acids to protect the intestinal mucosa and reduce the proliferation of bacteria responsible for intestinal inflammation.…”