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

Abstract

Introduction Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. Objective We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. Methods A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5–10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. Results The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. Conclusions Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.

Role of AHR Ligands in Skin Homeostasis and Cutaneous Inflammation

“…In vitro and in vivo studies with indirubin have reported its anti-inflammatory capacity [186,187]. Accordingly, this compound has been used in clinical trials for IBD treatment [188][189][190]. Additionally, since indigoids herbal remedies have been commonly used in traditional chinese medicine for treating dermatosis and skin lesions such as eczema, aphtha, or eruptions, a few clinical trials suggested that topical treatment with Indigo naturalis ointment is effective in treating PS [191,192] and AD [193].…”

Innate Lymphoid Cells as Regulators of Epithelial Integrity: Therapeutic Implications for Inflammatory Bowel Diseases

“…Similarly, indigo naturalis, which has been traditionally used in Chinese medicine, turned out to mediate its protective effect via AhR-mediated IL-22 production in ILC3s as well, resulting in reduced disease severity in several murine models of colitis ( 111 ). Moreover, especially a short-term treatment with indigo naturalis has been identified as effective treatment in patients with UC ( 112 ), whereas 8 weeks of administration cannot yet be fully excluded to potentially be associated with severe adverse events ( 113 ). Importantly, reduced AhR activation was observed in fecal samples from IBD compared to healthy subjects ( 110 ).…”

Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses

“…Its main bioactive components are the bis-indoles indigo and indirubin, which are formed by non-biological reactions during processing ( Sun et al, 2021 ). Therapeutic benefit of Indigo naturalis in ulcerative colitis (UC, a common inflammatory disease of the colon) was proven by recent clinical trials ( Naganuma et al, 2018 ; Naganuma et al, 2020 ; Uchiyama et al, 2020 ). Response rates for the herbal medicine were comparable to the most effective western drugs, including biologics that target TNFα, and patients whose disease was not well-managed by western drugs responded well to the herbal preparation ( Naganuma et al, 2020 ).…”