Ulcerative colitis(UC)is a chronic inflammatory disease of the gastrointestinal tract,which is closely related to gut barrier dysfunction.Emerging evidence shows that interleukin-22(IL-22)derived from group 3 innate lymphoid cells(ILC3s)confers benefits on intestinal barrier,and IL-22 expression is controlled by aryl hydrocarbon receptor(AhR).Previous studies show that baicalein protects the colon from inflammatory damage.In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice.Mice were administered baicalein(10,20,40 mg-kg-1-d-1,i.g.)for 10 days;the mice freely drank 3％dextran sulfate sodium(DSS)on D1-D7 to induce colitis.We showed that baicalein administration simultaneously ameliorated gut inflammation,decreased intestinal permeability,restored tight junctions of colons possibly via promoting AhR/IL-22 pathway.Co-administration of AhR antagonist CH223191(10mg/kg,i.p.)partially blocked the therapeutic effects of baicalein in colitis mice,whereas AhR agonist FICZ(1 μg,i.p.)ameliorated symptoms and gut barrier function in colitis mice.In a murine lymphocyte line MNK-3,baicalein(5-20 μM)dose-dependently increased the expression of AhR downstream target protein CYP1A1,and enhanced IL-22 production through facilitating AhR nuclear translocation,these effects were greatly diminished in shAhR-MNK3 cells,suggesting that baicalein induced IL-22 production in AhR-dependent manner.To further clarify that,we constructed an in vitro system consisting of MNK-3 and Caco-2 cells,in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells.In conclusion,this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s,thus providing a potential therapy for UC.

Yan-yang Li;Xiao-jing Wang;Yu-lin Su;Qing Wang;Shao-wei Huang;Zeng-feng Pan;Yan-ping Chen;Jun-jie Liang;Mei-ling Zhang;Xue-qian Xie;Zhi-yun Wu;Jin-yan Chen;Lian Zhou;Xia Luo

School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;College of Basic Medicine,Guangzhou University of Chinese Medicine,Guangzhou 510006,China

中国药理学报（英文版）

[1]Yan-yang Li;Xiao-jing Wang;Yu-lin Su;Qing Wang;Shao-wei Huang;Zeng-feng Pan;Yan-ping Chen;Jun-jie Liang;Mei-ling Zhang;Xue-qian Xie;Zhi-yun Wu;Jin-yan Chen;Lian Zhou;Xia Luo-.Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s)[J].中国药理学报（英文版）,2022(06):1495-1507

ILC3s,drank,colons,FICZ,shAhR,MNK3

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