Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

Naganuma, Makoto; Sugimoto, Seiichiro; Mitsuyama, Keiichi; Taku, Keisei; Yoshimura, Naoki; H, Ohi; Tanaka, Shinji; Andoh, Akira; Ohmiya, Naoki; Saigusa, Keiichiro; Yamamoto, Takayuki; Morohoshi, Yuichi; Ichikawa, Hitoshi; Matsuoka, Katsuyoshi; Hisamatsu, Tadakazu; Watanabe, Kenji; Mizuno, Shinta; Suda, Wataru; Hattori, Masahira; Fukuda, Shinji; Hirayama, Akiyoshi; Abe, Takayuki; Watanabe, Mamoru; Hibi, Toshifumi; Suzuki, Yasuo; Kanai, Takanori

doi:10.1053/j.gastro.2017.11.024

Cited by 156 publications

(161 citation statements)

References 33 publications

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“…Although the therapeutic efficacy of IN remains debatable, a recent multicenter randomized, double-blind, placebo-controlled study demonstrated its favorable therapeutic effects in inducing remission in UC. 11 The present study also showed that IN demonstrates a good therapeutic effect in inducing remission in UC. In addition, we also found a good maintenance effect of IN in UC.…”

Section: Discussionsupporting

confidence: 76%

“…In the present study, approximately half of the patients with UC were treated using 2.0 g/day, while the other half took 3.0 g/day for induction therapy. A recent randomized clinical trial for UC demonstrated a significant dose‐dependent linear trend in the clinical response at week 8 (placebo, 13.6%; 0.5 g/day, 69.6%; 1.0 g/day, 75.0%; 2.0 g, 81.0%) . In the present study, the therapeutic efficacy in inducing remission was comparable between UC patients treated using 2.0 g/day and those treated using 3.0 g/day (data not shown), and higher rates of clinical remission at weeks 4 and 8 might be attributed to the fact that larger doses of IN were administered.…”

Section: Discussionsupporting

confidence: 57%

“…In the present study, the therapeutic efficacy in inducing remission was comparable between UC patients treated using 2.0 g/day and those treated using 3.0 g/day (data not shown), and higher rates of clinical remission at weeks 4 and 8 might be attributed to the fact that larger doses of IN were administered. In contrast, the previously reported randomized clinical trial also demonstrated that clinical remission and mucosal healing rates at week 8 were highest in patients treated using 1.0 g/day . Therefore, further analysis is necessary regarding whether a smaller dose of IN, such as 1.0 g/day, is more appropriate for induction therapy in UC, because the current therapeutic goal is to achieve mucosal healing.…”

Section: Discussionmentioning

confidence: 87%

“…A pilot study targeting patients with moderately active UC demonstrated that following IN treatment, the rates of clinical response, clinical remission, and mucosal healing at week 8 were 72%, 33%, and 61%, respectively . In addition, a multicenter randomized, double‐blind, placebo‐controlled IN treatment study was recently conducted and significant therapeutic efficacy in inducing remission with a linear dose‐dependent trend was demonstrated . However, the clinical efficacy of IN as a maintenance therapy in UC remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

“…10 In addition, a multicenter randomized, double-blind, placebo-controlled IN treatment study was recently conducted and significant therapeutic efficacy in inducing remission with a linear dose-dependent trend was demonstrated. 11 However, the clinical efficacy of IN as a maintenance therapy in UC remains uncertain. In addition, no study has investigated the efficacy of IN in CD to date.…”

Section: Introductionmentioning

confidence: 99%

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Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

Matsuno

Hirano

Torisu

et al. 2019

J of Gastro and Hepatol

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Background and Aim Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. Methods Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan–Meier method. Overall adverse events (AEs) during follow‐up were also analyzed. Results Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non‐responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow‐up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. Conclusions Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

Matsuno

Hirano

Torisu

et al. 2019

J of Gastro and Hepatol

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Constructing multi‐enzymatic cascade reactions for selective production of 6‐bromoindirubin from tryptophan in Escherichia coli

Lee

Kim

et al. 2022

Biotech & Bioengineering

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6-Bromoindirubin (6BrIR), found in Murex sea snails, is a precursor of indirubinderivatives anticancer drugs. However, its synthesis remains limited due to uncharacterized biosynthetic pathways and difficulties in site-specific bromination and oxidation at the indole ring. Here, we present an efficient 6BrIR production strategy in Escherichia coli by using four enzymes, that is, tryptophan 6-halogenase fused with flavin reductase Fre (Fre-L3-SttH), tryptophanase (TnaA), toluene 4-monooxygenase (PmT4MO), and flavin-containing monooxygenase (MaFMO).Although most indole oxygenases preferentially oxygenate the electronically active C3 position of indole, PmT4MO was newly characterized to perform C2 oxygenation of 6-bromoindole with 45% yield to produce 6-bromo-2-oxindole. In addition, 6BrIR was selectively generated without indigo and indirubin byproducts by controlling the reducing power of cysteine and oxygen supply during the MaFMO reaction.These approaches led to 34.1 mg/L 6BrIR productions, making it possible to produce the critical precursor of the anticancer drugs only from natural ingredients such as tryptophan, NaBr, and oxygen.

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Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

Zhang¹,

Xu²,

Wu³

et al. 2020

Chemistry & Biodiversity

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Guchang Zhixie Wan (GZW) is a commonly used Chinese medicine for the treatment of ulcerative colitis (UC). This research explored the potential pharmacological mechanism of GZW in UC. The active ingredients, potential targets, and UC-related genes of GZW were retrieved from public databases. The pharmacological mechanisms including key components, potential targets and signal pathways were determined through bioinformatics analysis. The results of this study were verified through virtual molecular docking and cell experiments. Network analysis revealed that 26 active GZW compounds and 148 potential GZW target proteins were associated with UC. Quercetin, kaempferol and β-sitosterol were identified as the core active ingredients of GZW. IFNG, IL-1A, IL-1B, JUN, RELA, and STAT1 were indicated as key targets of GZW. These key targets have a strong affinity for quercetin, kaempferol, and β-sitosterol. GO and KEGG enrichment analysis showed that GZW target proteins are highly enriched in inflammatory, immune, and oxidative stress-related pathways. This study confirmed the therapeutic effect and revealed potential molecular mechanism of GZW on UC. And the protective effects of GZW on inflammatory bowel disease pathway were also revealed through STAT3/NF-кB/IL-6 pathway. The findings of this study enhanced our understanding of GZW in the treatment of UC and provided a feasible method for discovering potential drugs from traditional Chinese medicine formulations.

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Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis

Cited by 156 publications

References 33 publications

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

Short‐term and long‐term outcomes of indigo naturalis treatment for inflammatory bowel disease

Constructing multi‐enzymatic cascade reactions for selective production of 6‐bromoindirubin from tryptophan in Escherichia coli

Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

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