AUTHOR=Tang Qinglian , Jia Haidong , Qin Xu , Lu Zhaowen , Huang Wenjie , Wang Yujing , Cao Zhengyu 

TITLE=Scutellarein ameliorates dextran sulfate sodium-induced ulcerative colitis by inhibiting colonic epithelial cell proinflammation and barrier disruption

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1479441

DOI=10.3389/fphar.2024.1479441

ISSN=1663-9812

ABSTRACT=<sec><title>Introduction</title><p>Scutellarein (Scu) is a natural occurring flavonoid found in multiple traditional Chinese medicines such as <italic>Oroxylum</italic> indicum (L.) Kurz and <italic>Scutellaria baicalensis</italic>, with various pharmacological activities including anti-inflammation, anti-oxidation and myocardial protection. Here, we investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the underlying mechanism.</p></sec><sec><title>Methods</title><p>Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) induced colitis mouse model. Inflammation in colonic tissues was assessed by myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was used for mechanical investigation.</p></sec><sec><title>Results</title><p>Gavage of Scu significantly decreased the DAI score, improved colon shortening, ameliorated the pathological score in DSS-treated mice with better efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the expression levels of cytokines (<italic>Il-1β</italic>, <italic>Tnf-α</italic>, <italic>Il-1α</italic>, <italic>Il-6</italic>, and <italic>Cxcl1</italic>) as well as barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated expression levels of E-cadherin, occludin, and ZO-1, while reduced IL-1β-upregulated <italic>IL-6</italic> and <italic>IL-8</italic> mRNA levels. Moreover, Scu inhibited the phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and IL-1β-upregulated proinflammatory mediators expression in HT-29 cells.</p></sec><sec><title>Conclusion</title><p>These data demonstrate that Scu is an efficacious therapeutic agent to treat UC. Inhibition of inflammatory responses and maintenance of epithelial barrier integrity through NF-κB signaling pathway underlines Scu therapeutic effect on UC.</p></sec>