The purpose of this study was to assess the effect of NPI 32101 in a rat model of ulcerative colitis and the possible mechanisms of action of the effects observed. NPI 32101, 4 mg/kg intracolonically or 40 mg/kg orally, significantly reduced colonic inflammation compared to the placebo and no-treatment groups. Sulfasalazine (100 mg/kg), either intracolonically or orally, also reduced colonic inflammation.
NPI 32101 significantly suppressed the expression of matrix metalloproteinase (MMP)-9, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-12, whereas sulfasalazine suppressed MMP-9, IL-1β, and TNF-α, but not IL-12, compared to placebo. MMP-9 activity was reduced by NPI… 32101 and sulfasalazine.
NPI 32101 administered intracolonically or orally decreases ulcerative colitis in a rat model and is as effective as sulfasalazine. NPI 32101 treatment suppresses the expression and activity of MMP-9 and the expression of TNF-α, IL-1β, and IL-12, mechanisms by which NPI 32101 may exert its anti-inflammatory effects. NPI 32101 may have therapeutic potential for treatment of ulcerative colitis.