药理学
溃疡性结肠炎
代谢物
结肠炎
体内
化学
炎症
TLR4型
新陈代谢
生物化学
信号转导
医学
免疫学
生物
内科学
生物技术
疾病
作者
Mingfei Liu,Yuxuan Wang,Haixin Xiang,Meng Guo,Shirong Liu,Ming Liu,Jingchun Yao
出处
期刊:Molecules
[MDPI AG]
日期:2023-04-25
卷期号:28 (9): 3704-3704
被引量:5
标识
DOI:10.3390/molecules28093704
摘要
Ulcerative colitis (UC) has attracted much attention for its negative influence on quality of life and increased risk of colorectal cancer. Chemical and biological drugs are currently the usual treatment for UC. These drugs always induce severe side effects, or patients might become resistant to these therapies. Therefore, new therapeutic options for UC are urgently needed. In this study, we discovered the inhibitory activity of the intestinal tryptophan metabolite indole-3-carboxaldehyde (3-IAld) in dextran sulfate sodium salt (DSS)-induced UC mice by targeting the TLR4/NF-κB/p38 signaling pathway. This compound effectively protected against colon length shortening and damage induced by DSS in the colon, notably reducing the severity of inflammation. The production of inflammatory factors of TNF-α, IL-6, and IL-1β was significantly attenuated when treating with 3-IAld in vivo and vitro. This might be attributed to inhibition of the TLR4/NF-kB/p38 signaling pathway. Moreover, 3-IAld could up-regulate the expression of ZO-1 and Occludin in vivo and vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) results showed that 3-IAld could balance the aspartate and glutamate metabolism and the lysine degradation metabolism in the serum of DSS-induced colitis mice. In conclusion, 3-IAld ameliorated the intestinal barrier dysfunction and inflammatory response in DSS-induced UC mice, balanced amino acid metabolism, and inhibited the activation of the TLR4/NF-kB/p38 signaling pathway, thereby protecting mice with colitis.
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