Fig. 4. Comparative therapeutic effects of analogue 5 with treatments of reference on TNBS-induced acute colitis.

Acute colitis was induced in mice by intrarectal TNBS and the animals were then treated with analogue 5 (A5) or with treatments of reference (anti-TNFα antibody and Mesalazine) following the therapeutic regime indicated in the scheme (a). Mice injected intrarectally with 50% ethanol were used as basal controls. Animals injected with saline instead of A5 were used as untreated colitic mice. Disease evolution and severity were monitored by survival and weight loss, colitis score, macroscopic colon damage score and histopathological signs (b) and by measuring the cytokine levels in colonic mucosa (c). n = 8 mice/group in all assays, unless for histopathological analysis (n = 3 mice/group, where representative images are shown at ×100 magnification, scale bar: 200 µm). Data are mean ± SEM with dots representing individual values of biologically independent animals. Statistical differences between groups were calculated using two-tailed non-parametric Mann–Whitney test (for colon damage, colitis and microscopic scores), unpaired two-tailed Student’s t test (for body weight and colonic cytokines) and Kaplan–Meier test (for survival). ***p < 0.001; ****p < 0.0001 versus untreated TNBS-colitic mice (saline). Exact p-values are shown for p > 0.001. Source data are provided as a Source Data file. s.c. subcutaneous, i.v. intravenous, p.o. oral.