Fig. 8

UroA/UAS03 exert beneficial activities through AhR-dependent pathways. a–e Colitis was induced using TNBS in C57BL/6 (WT) and AhR^−/− mice (n = 4/group 7–8 week old age). Mice were treated with Veh or UroA/UAS03 (20 mg/kg bodyweight) every 12 h post TNBS administration and mice were euthanized at post 60 h TNBS administration. a TNBS-induced colitis experimental design and treatment regimen. b Percent body weight loss (No TNBS- Solid black line; Veh + TNBS- Solid red line; UroA + TNBS- Solid blue line; UAS03 + TNBS- Solid purple line), c representative colon images, d colon lengths, e gut permeability, f serum levels of IL-6 and TNF-α were determined. Statistical analysis was performed (unpaired t-test) using Graphpad Prism software. Error bars, ± SEM ***p < 0.001; **p < 0.01; *p < 0.05. g AhR-Nrf2 dependent tight junction protein regulation by UroA/UAS03. UroA/UAS03 (L:ligands) bind to AhR and activate its nuclear translocation to induce expression of Cyp1A1 and Nrf2. Further, UroA/UAS03 causes Nrf2-dependent upregulation of tight junction proteins and enhanced barrier function. h LPS (50 ng/ml)-induced IL-6 levels were measured in the presence of Vehicle or UroA or UAS03 (0.1, 1, 10, 20, 30, and 50 μM) in bone marrow derived macrophages (BMDM) from wild type (WT), Nrf2^−/− and AhR^−/− mice. The data is representative of two independent experiments with triplicates. Statistical analysis was performed (unpaired t-test) using Graphpad Prism software. Error bars, ±SEM ***p < 0.001; **p < 0.01 *p < 0.05. Source Data are provided as a Source Data File