| Although biologics are useful for refractory ulcerative colitis (UC) patients, intractable cases, some patients do not have any efficacies even the advanced anti-inflammatory therapies are given. We recently performed a randomized controlled trial to investigate clinical and endoscopic efficacy of indigo naturalis (IN), aryl hydrocarbon receptor ligand, in UC patients. Before clinical trial, we confirmed that IN ameliorated the DSS-induced colitis and suppressed the expression of pro-inflammatory cytokines. IN also decreased the size of colitis-associated carcinoma in mouse model. In a multicenter, double-blind trial, we confirmed that 8-weeks treatment of IN obtained significant clinical effects as the proportion of patients with clinical response was significantly higher (p<0.001) in 0.5 (70%), 1.0g (75%), and 2.0 (81%) IN group than that in placebo group(14%). The MH rates were 14%, 57% (P=0.005), 60% (P=0.003) and 48% (P=0.02) in placebo and 0.5, 1.0, and 2.0 g group, respectively. Although mild liver dysfunction was observed in 10 patients who received IN, all cases were recovered and no serious adverse events were observed. IN is an effective treatment for patients with active UC, and the efficacy was even confirmed in patients who received the lowest dose of IN. However, pulmonary arterial hypertension was reported in a patient who used self-purchased IN (not in our study). Therefore, adverse events due to IN are concerned and further promotion of animal experiments, elucidation of the mechanisms underlying the adverse events and their appropriate monitoring may be mandatory to proceed further development of IN. |
