Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis

Abstract

Background: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. Objectives: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. Method:We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. Re-sults: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. Conclusions:We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.

Indigo Naturalis Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Intestinal Microbiota Community

“…Although IN exhibited significant clinical and endoscopic efficacy in treating colitis without causing serious adverse side effects [43,44], the concrete mechanisms of IN remain elusive [28]. The poor water solubility of IN greatly affects the absorption of its oral treatment in colitis.…”

Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial

“…Although there have been some reports on the efficacy of Chinese herbal medicines, including IN and Xileisan, for active UC [2][3][4][5], the mechanisms of their therapeutic effects remain unknown. It has been reported that the effect on Crohn's disease was not as high as on UC [10].…”

“…In Japan, IN powder has been sold as a health food, and its efficacy has been widely known in some UC patients. Then, some case reports that revealed the efficacy of IN for UC were published [2][3][4]. Additionally, the Chinese herbal medicine Xileisan enema, which is mainly composed of IN, is used to treat ulcerative enteritis in China, and the effectiveness of suppositories has been reported in Japan [5].…”

Suppository treatment in ulcerative proctitis

“…Besides, a single-agent Indigo Naturalis (IN) suppository was evaluated by Yoshimatsu et al 43 in an open-label, single-center, prospective pilot study. A total of 10 patients, who were refractory to topical mesalamine or corticosteroids, were treated with 50 mg IN QD for 4 weeks.…”