Treatment-refractory ulcerative colitis responsive to indigo naturalis

Area of Science:

• Gastroenterology
• Pharmacology
• Immunology

Background:

• Indigo naturalis (IN) is an herbal medicine used for ulcerative colitis (UC).
• Its mechanism of action is unclear, but key components indigo and indirubin activate the aryl hydrocarbon receptor (AhR).
• This study investigates IN's safety, efficacy, and AhR activity in UC patients.

Purpose of the Study:

• To assess the safety and efficacy of oral Indigo naturalis (IN) in patients with treatment-refractory ulcerative colitis (UC).
• To evaluate the impact of IN on colon aryl hydrocarbon receptor (AhR) activity.
• To explore the role of AhR in IN's therapeutic effects using an AhR antagonist in a murine colitis model.

Main Methods:

• An open-label, dose-escalation study treated 11 UC patients with IN (500 mg/day or 1.5 g/day) for 8 weeks.
• Efficacy was measured by clinical response (total Mayo score), remission, endoscopic severity, and quality of life.
• Colon AhR activity was assessed via cytochrome P450 1A1 (CYP1A1) RNA expression.

Main Results:

• 91% of patients achieved clinical response, including those refractory to conventional therapies and biologics.
• Three patients achieved clinical remission, and all showed improved endoscopic scores and quality of life.
• Colon CYP1A1 RNA expression increased significantly, and an AhR antagonist blocked IN's benefits in a mouse model.

Conclusions:

• Indigo naturalis (IN) appears to be a safe and effective therapy for treatment-refractory ulcerative colitis.
• The therapeutic benefits of IN are likely mediated through the activation of the aryl hydrocarbon receptor (AhR).