Tilapia head glycolipids protect mice against dextran sulfate sodium-induced colitis by ameliorating the gut barrier and suppressing NF-kappa B signaling pathway.

The purpose of this study was to evaluate the relieving effect of tilapia head glycolipids (TH-GLs) on dextran sulfate sodium (DSS)-induced colitis in mice and to further explore its mechanism. Mice were orally administered 3% (w/v) DSS to establish a model of ulcerative colitis (UC), and subsequently treated with TH-GLs or sulfasalazine. In addition, the expression of key targets in the intestinal mucosal barrier and the inflammatory signal pathway were studied by combining immunochemical analysis techniques. The results showed that varying doses of TH-GLs can significantly improve colon lesions caused by DSS, reduce histological scores, increase mucus secretion, extend colon length, increase weight, and inhibit the occurrence of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), Interleukin-1β (IL-1β), and Interleukin- 6 (IL-6). Further, studies have shown that TH-GLs increase the secretion of MUC2 and up-regulate the expression of tight junction related proteins, such as ZO-1 and Occludin. In addition, TH-GLs significantly down-regulated the protein expression levels of TNF-α, IKK-β, and nuclear factor-κB (NF-κB). Here, we have elucidated the potential mechanism of TH-GLs in protecting mice with colitis. In general, this study shows that TH-GLs could improve the symptoms of UC by improving the gut barrier and inhibiting inflammatory signals, which provides a scientific basis for future clinical applications.

Gu Z ，Zhu Y ，Mei F ，Dong X ，Xia G ，Shen X ... -  《-》

Tilapia head glycolipids reduce inflammation by regulating the gut microbiota in dextran sulphate sodium-induced colitis mice.

Gu Z ，Zhu Y ，Jiang S ，Xia G ，Li C ，Zhang X ，Zhang J ，Shen X ... -  《-》

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Wu H ，Chen QY ，Wang WZ ，Chu S ，Liu XX ，Liu YJ ，Tan C ，Zhu F ，Deng SJ ，Dong YL ，Yu T ，Gao F ，He HX ，Leng XY ，Fan H ... -  《-》

Astragalin Attenuates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting NF-κB Activation in Mice.

With the ulcerative colitis (UC) incidence increasing worldwide, it is of great importance to prevent and treat UC. However, efficient treatment options for UC are relatively limited. Due to the potentially serious adverse effects of existing drugs, there is an increasing demand for alternative candidate resources derived from natural and functional foods. Astragalin (AG) is a type of anti-inflammatory flavonoid, with Moringa oleifera and Cassia alata being its main sources. In this study, we investigated the therapeutic effects of AG on mice with dextran sulfate sodium (DSS)-induced colitis. Our results suggested that AG treatment reduced weight loss and the disease activity index (DAI), prevented colon shortening and alleviated colonic tissue damage. AG treatment reduced the expression of pro-inflammatory cytokines and related mRNAs (such as TNF-α, IL-6, and IL-1β), inhibited colonic infiltration by macrophages and neutrophils, ameliorated metabolic endotoxemia, and improved intestinal mucosal barrier function (increased expression levels of mRNAs such as ZO-1, occludin, and Muc2). Western blot analysis revealed that AG downregulated the NF-κB signaling pathway. Moreover, AG treatment partially reversed the alterations in the gut microbiota in colitis mice, mainly by increasing the abundance of potentially beneficial bacteria (such as Ruminococcaceae) and decreasing the abundance of potentially harmful bacteria (such as Escherichia-Shigella). Ruminococcaceae and Enterobacteriaceae (Escherichia-Shigella) were thought to be the key groups affected by AG to improve UC. Therefore, AG might exert a good anti-UC effect through microbiota/LPS/TLR4/NF-kB-related pathways in mice. The results of this study reveal the anti-inflammatory effect and mechanism of AG and provide an important reference for studying the mechanisms of natural flavonoids involved in preventing inflammation-driven diseases.

Peng L ，Gao X ，Nie L ，Xie J ，Dai T ，Shi C ，Tao L ，Wang Y ，Tian Y ，Sheng J ... -  《Frontiers in Immunology》

Protective effects of Lizhong decoction on ulcerative colitis in mice by suppressing inflammation and ameliorating gut barrier.

Lizhong Decoction (LZD) is a classical prescription firstly recorded in "Shanghan Lun". It has been used to clinically treat ulcerative colitis (UC) for thousands of years. However, its mechanism is not clear up to now. The goal of this study was to assess the amelioration of LZD on dextran sodium sulfate (DSS)-induced colitis in mice and further clarify its mechanism. The ulcerative colitis model induced by DSS was successfully established and applied to evaluate the intervention effect after oral administration of LZD. Furthermore, the expression of key targets in inflammatory signaling pathways and intestinal tight junction proteins were investigated by enzyme-linked immunosorbent assay (ELISA) and quantitative real time polymerase chain reaction (qPCR) analysis. The results showed that all doses of LZD could notably improve DSS-induced colon lesions, reduce histological scores, prolong colon length and increase body weight. Colonic inflammation in UC mice was significantly alleviated by inhibiting the activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), reducing the yield of nitric oxide (NO) and inflammatory cytokines such as interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and along with promoting the production of anti-inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10) after LZD treatment. Furthermore, LZD remarkably down-regulated the level of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) mRNA and up-regulated the expression of tight junction proteins (zonula occluden-1, occludin and claudin-1) in UC mice. In summary, this study indicated that LZD could notably improve UC symptoms by suppressing inflammation and ameliorating gut barrier, which provided scientific basis for its clinical application in the future.

Shen Y ，Zou J ，Chen M ，Zhang Z ，Liu C ，Jiang S ，Qian D ，Duan JA ... -  《-》