indigo naturalis enema

Cited by lists all citing articles based on Crossref citations.Articles with the Crossref icon will open in a new tab. More recently, Matsuno etal also reported on two cases of IN-induced colitis [33]. Schroeder KW, Tremaine WJ, Ilstrup DM: Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. Indigo and indirubin, the active components of IN, have an indole ring in their chemical structure. N Engl J Med 2005;353:2462-2476. Stockinger B, Di Meglio P, Gialitakis M, Duarte JH: The aryl hydrocarbon receptor: multitasking in the immune system. Treatment with indigo naturalis for infl . 2. Nature 2008;453:106-109. A recent study indicates that CARD 9 contributes to promotion IL-22 release and thus promotes recovery from colitis. For gastrointestinal diseases, Yuan et al. In the near future, the mechanism that underlies the adverse effects of IN needs to be determined, and extraction of active ingredients with fewer side effects, investigated. This study also confirmed that the efficacies of refined and crude IN ointments were comparable [39]. Patient masking and direct comparison with a current treatment control group are lacking. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL: Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Number of Figures: 4 3a). Inflamm Bowel Dis 2006;12:328-333. Nature 2008;453:65-71. Conclusion: This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine. However, it is critical to assess the safety of capsuled (exact 2 g daily) Qing-Dai in the small study to conduct large randomized controlled trial in the future. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Although the efficacy of IN was confirmed for UC, whether IN is effective for CD is unclear. Main endpoints of the INDIGO study. When ingested, I3C reacts with gastric acid to form 6-formylindolo [3,2-b] carbazole (FICZ). Five (25%) patients did not respond, and 1 (5%) patient discontinued the use of Qing-Dai due to infectious colitis, although she wished to continue this trial due to her initial response to Qing-Dai. Lancet 2012;380:1606-1619. Aliment Pharmacol Ther 2009;30:126-137. In mouse model, Monteleone, etal. World J Gastroenterol 2002;8:158-161. [20] have reported that Qing-Dai is clinically efficacious and safe in treating UC patients, although the data collected were retrospective in nature. Ogata H, Kato J, Hirai F, Hida N, Matsui T, Matsumoto T, Koyanagi K, Hibi T: Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis. Although IN is effective even for refractory cases, critical adverse effects including IN-induced colitis and pulmonary arterial hypertension should be concerned. Therefore, AhR-related compounds have a protective mechanism implemented through the 3-IAld/AhR/IL-22/IL-10 axis that can be therapeutically useful in treating UC patients. At the entries, the mean age was 38.7 (range 22-80 years), and the mean duration of the disease was 8.0 years (range 2-21 years). Ords I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ: Ulcerative colitis. Additional reports have been published on the Chinese herbal medicine Xilei-San [24,25,26], Kui Jie Qing enema [27] and Fufangkushen colon-coated capsules [28]. Zelante T, Iannitti RG, Fallarino F, Gargaro M, De Luca A, Moretti S, Bartoli A, Romani L: Tryptophan feeding of the IDO1-AhR axis in host-microbial symbiosis. These results suggest a role of IN that includes AhR ligands produced by intestinal bacteria. The most important finding in our prospective study is that oral capsule Qing-Dai is remarkably effective for inducing remission in patients with moderate UC activity even compared to other well-known approved medicines; thus, Qing-Dai may be a therapeutic option for these patients. This pilot, exploratory study was limited in size, and the scope of this study was to evaluate the efficacy and safety of capsuled Qing-Dai for patients with UC for deciding the sample size of randomized controlled trial in the future. A link to reset your password has been sent to your e-mail address. Yuan et al. N Engl J Med 1987;317:1625-1629. IN also suppresses LPS-induced production of TNF- and IL-6 in vitro. Gisbert JP, Linares PM, McNicholl AG, Mat J, Gomolln F: Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. IL-22 also regulates the release of antimicrobial peptides, such as calprotectin, S100A8, and S100A9, which have anti-inflammatory effects [35]. It may also be necessary to develop medications that are not absorbed in the small intestine to alleviate adverse effects. Evid Based Complement Alternat Med 2014;2014:569587. Fhang etal reported a case of ischemic colitis induced by IN; the patient was successfully treated using laparoscopic sigmoid colectomy, and pathological examination revealed ischemic or toxic injury of the sigmoid colon [32]. More recently, a suppository form of IN has been used in a clinical trial to confirm the safety and efficacy of rectal IN for active UC. Since Qing-Dai appears dark blue, it was difficult to perform a placebo-controlled trial with the powder form. Aliment Pharmacol Ther 2013;38:854-863. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. Each 10 patients were classified as having extensive or left-sided colitis, respectively. Suzuki et al. Ulcerative colitis (UC) is an immune-mediated intestinal disease characterized by periods of remission and relapse [1]. In this study, the rate of clinical remission at Day 14 was significantly higher in patients receiving rectal Xilei-San than for patients receiving a placebo. Annu Rev Immunol 2014;32:403-432. The UCEIS improved from a mean of 5.0 (with a score of 2 in 1 patient, 4 in 4 patients, 5 in 8 patients, 6 in 3 patients, and 7 in 2 patients) to a mean of 2.4 (with a score of 1 in 4 patient, 2 in 7 patients, 3 in 3 patients, and 4 in 4 patients (p < 0.001; fig. Using a refined formulation (Lindioil), a recent report indicated that Lindioil ointment is more effective than vehicle for the treatment of nail psoriasis [10]. The patients' demographic data and disease characteristics were collected. After analyzing the data of 10 patients, we added 10 more patients predominantly for safety reasons. J Dig Dis 2008;9:52-62. Chinese Cooperative Group for the Study on IBD; Chinese Society of Gastroenterology, Ouyang Q, Hu PJ, Qian JM, Zheng JJ, Hu RW: Consensus on the management of inflammatory bowel disease in China in 2007. Follow the instructions and try to log in again. Inflamm Bowel Dis 2012;18:803-808. The secondary efficacy endpoint was the rate of clinical remission and mucosal healing at 8 weeks of treatment (last survey point). ; a multicenter RCT is needed in the near future. We were especially concerned about liver dysfunction because of the well-known toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through the aryl hydrocarbon receptor (AhR) signaling [13]. Because indirubin, the active component of indigo naturalis, is an effective component of IN, it may be a safe alternative for topical treatment of psoriasis, which is quite different from topical corticosteroids [41]. Although 8 of 9 patients of this study previously received corticosteroid, azathioprine, or anti-TNFtreatment before initiation of IN therapy, the efficacy of IN was satisfactory for these refractory cases. The oral or topical products of Qing-Dai are known to be effective and safe treatment options for psoriasis [16,17,18]. The serial changes in Mayo score, partial Mayo score, and endoscopic scores (Mayo endoscopic score and UCEIS) were also assessed. Recent reports have indicated that IN induces critical adverse effects, such as liver dysfunction, severe colitis, and PAH. Table 3 summarizes the clinical use of IN for psoriasis. In this study, 30 patients with intractable ulcerative proctitis were randomized to receive either Xilei-San or placebo suppositories for 2 weeks. The mechanisms of IN for UC is not clear, but aryl hydrocarbon receptor ligand, the active components of IN, can promote mucosal healing by inducing the production of interleukin-22 from type-3 innate lymphocytes cells. The clinical manifestations of TCDD exposure include progressive liver or renal failure, emphysema, and myocardial degeneration [13]. The fundamental treatment for UC is administration of 5-aminosalicylic acid and a corticosteroid. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. The venous blood samples were obtained from each patient at weeks 0 (pretreatment), 4 and 8. Gastroenterology 2015;148:1035-1058.e3. In addition, indole-3-carboxaldehyde (IAld) is produced from tryptophan by intestinal bacteria. However, purified natural products as ingredients are preferable, rather than crude extracts, to manufacture high-quality medications. Immunosuppressants, such as cyclosporine [7] and tacrolimus [8], and anti-tumor necrosis factor (TNF)- agents, such as infliximab [9] and adalimumab [10], are available for corticosteroid-refractory UC with moderate-to-severe activity; however, prior loss of response or intolerance to these agents and infection due to immunosuppression are increasingly becoming clinical problems [6]. The clinical response was defined as a decrease in the Mayo score of 1 in each item. Summary of the clinical efficacy of medical treatments for UC patients. Although 60% of patients were refractory cases, 72% of patients receiving IN obtained clinical response by week 8. Clinical endoscopic examples of before and after treatment with Qing-Dai (representative 5 cases). Two patients were treated with infliximab for over the past 1 year, but were currently at the condition of secondary failure; they discontinued its use over 4 weeks before the entry. However, Qing-Dai was continued in these 2 patients, and AST/ALT was not significantly increased at week 8. Gastroenterology 2013;145:987-995. Natura-alpha (meisoindigo; N-methyl-3,3-dihydroindole-2,2diketone), an indirubin derivative, is a synthetic small molecule oral compound, which is believed to inhibit the expression of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-, and to block inflammatory cytokines by stimulating the production of IL-10 [37]. received lecture fees from Takeda Pharmaceutical Co., Ltd. However, published data on the efficacy of Qing-Dai for UC patients are mostly lacking in the English literature. D'Haens G, Sandborn WJ, Feagan BG, Geboes K, Hanauer SB, Irvine EJ, Lmann M, Marteau P, Rutgeerts P, Schlmerich J, Sutherland LR: A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Another is tofacitinib, which inhibits Janus kinase (JAK) 1, 2 and 3, resulting in suppression of several cytokines [11]. It is not clear whether the efficacy of IN is comparable to traditional medicine for patients with IBD and other inflammatory disorders. For patients who are refractory to or dependent on steroids, cytapheresis treatment, thiopurine, immunosuppressants, and anti-TNF treatments are used [29]. Eur J Integr Med 2014;6:135-146. Front Immunol 2014;5:640. reported a case of PAH in a patient who received 2g of IN daily for 6 months [34]. Many refractory patients may be helped by IN if it becomes available in appropriate forms for clinical practice. Existing medications mainly act on the immune system and do not target epithelial regeneration. Fukunaga K, Hida N, Ohnishi K, Ohda Y, Yoshida K, Kusaka T, Jinno Y, Nagase K, Nakamura S, Kadobayashi M, Miwa H, Matsumoto T: A suppository Chinese medicine (xilei-san) for refractory ulcerative proctitis: a pilot clinical trial. The serum albumin level also improved from 3.9 to 4.4 mg/ml (p = 0.001). The pathophysiology of IBD has been extensively studied and genetic and environmental factors and dysregulation of the immune system have been found to be involved. A total of 20 patients with mild-to-moderate UC activity were administered 2g of IN daily for 8 weeks. Register to receive personalised research and resources by email. Gastroenterology 2007;132:763-786. Wang B, Ren S, Feng W, Zhong Z, Qin C: Kui jie qing in the treatment of chronic non-specific ulcerative colitis. National surveillance data for PAH induced by IN is available and analysis of these data is ongoing. Commensal bacteria utilize tryptophan as an energy source and produce 3-IAld [15]. The major goal of UC treatment is to induce and maintain remission to alleviate symptoms and promote mucosal healing, which is associated with a favorable long-term prognosis [2]. The herbal medicine Qing-Dai (also known as indigo naturalis) is extracted from plants, such as Indigofera tinctoria, Isatis tinctoria, and Polygonum tinctorium. However, 10% of reversible liver dysfunction may be considered to be a high rate. Suzuki H, Kaneko T, Mizokami Y, Narasaka T, Endo S, Matsui H, Yanaka A, Hirayama A, Hyodo I: Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis. This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply. We might have considered treatment with corticosteroid or tacrolimus if 20 patients had not registered for enrollment in this study; thus, Qing-Dai was considered an alternative treatment to avoid the use of corticosteroids or other immunosuppressants. The changes in scores and laboratory results were evaluated by Wilcoxon signed-rank test. 20140253). IN made from Fujian is regarded as being of the highest quality [15]. The serum CRP level was significantly improved from a mean of 0.60 mg/dl to a mean of 0.20 mg/dl (p = 0.02) by treatment with Qing-Dai. IN-induced colitis may be more likely to occur in right colon because IN tends to be stored in this region. The mean fecal immunological quantitative test decreased at 8 weeks after treatment with Qing-Dai (2,433 3,002 ng/ml to 420 533 ng/ml, p < 0.001). Zhang F, Li Y, Xu F, Chu Y, Zhao W: Comparison of Xilei-san, a Chinese herbal medicine, and dexamethasone in mild/moderate ulcerative proctitis: a double-blind randomized clinical trial. 2016 The Author(s) Published by S. Karger AG, Basel. No patient developed a severe exacerbation requiring hospitalization over the 8-week period nor did any patient start biologics. To address these concerns, new medication needs to be developed by devising drug delivery system. Can Qing-Dai be used for treating patients with Crohn's disease or Behet's disease? The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. Ng SC, Lam YT, Tsoi KK, Chan FK, Sung JJ, Wu JC: Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. The Mayo score significantly improved from a mean of 7.9 to a mean of 2.7 (p < 0.001; fig. Few direct studies in human subjects have addressed IN inhibition of colitis via promoting IL-22. Overall, the clinical scores were significantly decreased by treatment with Qing-Dai. In fact, crude drug is usually difficult to get approved as a drug in Japan and in Western countries. 3b) and from 9.4 to 3.5 (p < 0.001; fig. After 6 months, the rate of recurrence was lower in the group of Xilei-San (Xilei-San 18.2% vs. placebo 83.3%, p < 0.001) [25]. The patients were not treated with infliximab within 4 weeks before the commencement of the study. Our study intended to use single herbal formulas rather than multiple herbal formulas. A recent study indicates that IN significantly reduces the disease activity index and colonic myeloperoxidase activity of in a DSS colitis model [16]. Two-sided p values were considered to be statistically significant at a level of <0.05. Concomitant treatment with thiopurine, started more than 12 weeks before the commencement of the study, was allowed if that dosage had been stable for at least 4 weeks before the study was conducted. The mechanism of liver dysfunction is not clear; it may be related to induction of CYP1A1 in the liver [12]. In 1 patient (infectious colitis), the administration of the test agent was ceased at symptom onset (32 days after treatment). In the near future, the efficacy of IN for refractory cases should be confirmed in a large control study. World J Gastroenterol 2013;19:2718-2722. Four 250-mg capsules of Qing-Dai were taken by patients twice a day (daily dose, 2 g) for 8 weeks. In conclusion, we prospectively showed significant clinical and endoscopic response in UC patients treated with oral Qing-Dai at 8 weeks. Importantly, no significant adverse side effects were observed in either study [25,26]. Lin YK, Leu YL, Huang TH, Wu YH, Chung PJ, Su Pang JH, Hwang TL: Anti-inflammatory effects of the extract of indigo naturalis in human neutrophils. Fukunaga K, Ohda Y, Hida N, Iimuro M, Yokoyama Y, Kamikozuru K, Nagase K, Nakamura S, Miwa H, Matsumoto T: Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis. Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S: Cyclosporine in severe ulcerative colitis refractory to steroid therapy. These treatments are multiple herbal formulas that partly contain Qing-Dai. contributed equally to this work. CD is characterized by transmural inflammation in the gut. In China, IN is quality controlled as an herbal medicine containing more than 2.0% indigo and more than 0.13% indirubin. These liver dysfunctions were reversible after the test was completed, suggesting that they were side effects of Qing-Dai. A recent study also indicates that IN shows a therapeutic effect on intestinal inflammation in a DSS colitis mouse model, and this effect was not observed in Ahr-deficient mice. Mainly, IN is used as a topical therapy for psoriasis to reduce the production of toxic metabolites [36]. Issue release date: June 2016, Number of Print Pages: 9 Two patients with liver dysfunction, 1 patient with infectious colitis, 2 patients with mild transient headache and 1 patient with mild nausea were reported during the test period. Mucosal Immunol 2010;3:361-373. This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). An important group of natural AhR ligands is indole, such as indole-3-aldehyde (3-IAld), indole-3-acetaldehyde, indole-3-acetic acid and indole-3-lactic acid, which can be generated by the bacterial metabolism of tryptophan and are also derived from the metabolism of dietary intake [13,14]. This work was supported in part by Health and Labour, Sciences Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan. Clinical response was defined as a decrease in the Mayo score of 1 in each item. The duration of active treatment was 4weeks in this trial, yet remission was maintained at Day 180 for 81.8% of patients receiving active treatment while only 16.7% of patients who received the placebo remained in remission. Adverse effects, including PAH, are described at the next section. One was a case of colitis with wall thickness of the ascending colon and an ileocecal intussusception and the other was a case of colitis with marked wall thickening of the right colon. A phase II trial (ClinicalTrials.gov identifier: NCT01216280) of Natura-alpha is currently underway for the treatment of moderate-to-severe UC patients. In this study, we demonstrated that a traditional Chinese medicine Qing-Dai is overall safe and effective for the induction of remission in UC patients. Privacy Policy | Terms of Use | Imprint | Cookies. J Ethnopharmacol 2012;141:592-598. Rahimi R, Nikfar S, Abdollahi M: Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: a meta-analysis. J Clin Oncol 2009;8:114-116. IN displays important activity by repairing colonic mucosa in aryl hydrocarbon receptor signaling involved in maintenance of homeostasis and mucosal immunity. IN is a herbal medicine extracted from leaves and stems of plants such as Indigofera tinctoria, Strobilanthes cusia O Kuntze, and Polygonum tinctorium Lour. The efficacy of IN for active UC was also objectively confirmed using fecal biomarkers, such as fecal calprotectin. Powdered Qing-Dai imported from Fujian, China was purchased from Uchidawakanyaku, Ltd. (Tokyo, Japan). While AhR has been shown to promote IL-17 expression in vitro [31,32], the AhR signaling pathway suppresses Th17 cell differentiation in vivo [15,33]. However, some patients do not respond to this regimen, and approximately 30% of patients who receive corticosteroids become steroid-dependent [1]. Am J Gastroenterol 2011;106:590-599. The CRP levels and quantitative fecal occult blood tests at 8 weeks were compared with those at baseline. The major goal of therapy in UC is to induce and maintain remission [2]. After the patient was diagnosed with PAH, IN was discontinued. Recently, Qing-Dai (Indigo naturalis, IN), which is a component of crude drugs used in China, was reported to be effective for treating UC. Patients who were aged 20, who had mild-to-moderate UC activity and were diagnosed according to the diagnostic criteria defined by the research group of inflammatory bowel disease in the Ministry of Health, Labor and Welfare in Japan were eligible to participate in this open-label, prospective study. Although corticosteroids, anti-TNF agents and calcineurin inhibitors are effective for inducing clinical remission, these medications have produced no response in several patients. It is particularly efficacious for otherwise refractory cases [1214]. In 1 patient, the administration of the test agent was ceased due to mild nausea considered side effects of Qing-Dai (5 days after treatment), and she wanted to change treatment to granulocytapheresis. I3C is abundant in green-yellow vegetables [15]. The first patient was enrolled in March 2015, and the last patient completed the trial in December 2015. a Mayo score (p < 0.001); b partial Mayo score (p < 0.001); c CAI (p < 0.001); d Mayo endoscopic score (p < 0.001); e UCEIS scores (p < 0.001) were significantly decreased at 8 weeks after treatment with Qing-Dai. The first study to demonstrate the efficacy of oral IN was published by a Japanese group. This study was pre-registered at the University Hospital Medical Information Network Center (UMIN Clinical Trials Registry, number UMIN000016526; available at http://www.umin.ac.jp/ctr/). Suzuki etal. As shown in figure 2, 6 (30%) patients achieved clinical remission, and additionally 7 (35%) patients showed clinical response at 8 weeks. To learn about our use of cookies and how you can manage your cookie settings, please see our Cookie Policy. Traditionally, Qing-Dai has been used in Chinese medicine to treat UC patients; however, published data on the safety and efficacy of Qing-Dai for UC patients are lacking in the English literature. IN and Xilei-San are used topically in China, because oral treatment may cause liver dysfunction, headache, and nausea [13,14]. Three patients were treated with adalimumab for over the past 1 year, but were currently at the condition of secondary failure; they discontinued its use 2 weeks before the entry. 3c), respectively. It is not clear whether IN suppresses proinflammatory cytokines release directly or whether suppression is merely a result reduced inflammation. According to a report of Chinese UC patients treated from 1981 to 2000, 20.1% of UC patients were treated with only Chinese herbs, and 59.1% were treated with a combined Chinese and western medicine approach [11]. The current pharmacologic management of UC has relied primarily on mesalamine [3], corticosteroids [4], and thiopurines [5]. A review. We use cookies to improve your website experience. A total of 20 patients (10 male and 10 female) with moderate UC activity were included in the study. reported that IN ointment prepared by mixing IN powder with olive oil, filtering, and then mixing with petroleum jelly and wax was effective for patients with psoriasis in clinical trials. Did you know that with a free Taylor & Francis Online account you can gain access to the following benefits? World J Gastroenterol 2013;19:5738-5749. The adverse side effects of Qing-Dai are typically diarrhea, abdominal pain, nausea, vomiting, liver dysfunction, cutaneous symptoms, leukocyte decrease, dizziness and headache [18,30]. CARD 9 is a susceptibility gene for IBD. UC did become worse after discontinuation of IN therapy [35]. Topical and oral Qing-Dai are used to treat various inflammatory diseases and dermatosis, such as psoriasis [16,17,18].