sauchinone and Colitis

Inflammatory bowel disease (IBD) is characterized by chronic, unpredictable relapsing and inflammatory disease of the gastrointestinal tract. Daily diet patterns have long been one of the most important hotspots for IBD therapeutic strategies. Sauchinone (SAU), a key bioactive lignin isolated from the roots of the herb Saururus chinensis, has been known to play an anti-inflammatory role in several diseases. However, its effect on IBD has not yet been investigated. In the current study, we established 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and treated them with SAU. Flow cytometric analysis was performed to determine the phenotype of T cells in the lamina propria. qRT-PCR and ELISA were performed to measure cytokine transcript and protein levels, respectively. We found that SAU ameliorated TNBS-induced mouse colitis and inflammatory responses in mucosal tissues and peripheral blood CD4

Topics: Animals; Benzopyrans; Colitis; Dioxoles; Humans; Inflammation; Inflammatory Bowel Diseases; Interleukin-10; Intestines; Mice; Positive Regulatory Domain I-Binding Factor 1; Signal Transduction; Th17 Cells; Trinitrobenzenesulfonic Acid

The pathogenesis of inflammation bowel disease (IBD) involves exaggerated effector T cell responses and impaired regulatory T cell functions. We previously found that sauchinone (SAU) ameliorated experimental colitis via facilitating Th17 cell production of IL-10, but how SAU regulated Th17 cell differentiation remains unknown. MicroRNAs (miR) have been recognized as a crucial regulator of T cell biology and play a considerable role in IBD. Here, we demonstrated that SAU significantly suppressed miR-340 expression in Th17 cells, and enforced miR-340 expression abrogated SAU inhibition of Th17 differentiation. miR-340 itself was found to facilitate Th17 differentiation, especially the pathogenic "Th1-like" subset. In human IBD, miR-340 was intimately correlated with the disease severity. SAU markedly decreased miR-340 in the inflamed mucosa tissues from IBD patients. Scaffold/matrix-associated region-binding protein 1 (SMAR1) was identified as a target gene of miR-340. We revealed that blockade of miR-340 significantly reduced mucosal damage and Th17 responses in the lamina propria in a mouse colitis model. Our findings suggest that miR-340 negatively affects SAU inhibition of Th17 differentiation and might play a crucial role in the regulation of pathogenic "Th1-like" Th17 cell generation, which might serve as a novel therapeutic target of IBD.

Topics: Base Sequence; Benzopyrans; Cell Cycle Proteins; Cell Differentiation; Colitis; Dioxoles; Disease Susceptibility; DNA-Binding Proteins; Down-Regulation; Forkhead Transcription Factors; Humans; Inflammation; Inflammatory Bowel Diseases; Intestines; MicroRNAs; Nuclear Proteins; Severity of Illness Index; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Trinitrobenzenesulfonic Acid; Up-Regulation

Topics: Animals; Anti-Inflammatory Agents; Benzopyrans; Colitis; Dendritic Cells; Dextran Sulfate; Dioxoles; Inflammation; Male; Mice, Inbred C57BL; Positive Regulatory Domain I-Binding Factor 1; Th17 Cells