indigo-carmine and Colitis

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Indigo Carmine; Mice; Reactive Oxygen Species

Indigo (IND) and indirubin (INB) have demonstrated a synergistic effect in treating ulcerative colitis at a ratio of 7.5:1. However, the colon mucus layer, a critical physiological barrier against external threats, is also a biological barrier, limiting the potential for effective drug delivery to the lamina propria for regulating inflammatory cells. Inspired by the potential of Hyaluronic acid (HA), to enhance cellular uptake by inflammatory cells, and Pluronic® F127 (F127), known for overcoming the mucus barrier, this study innovatively developed INB/IND nanosuspensions by co-modifying with F127 and HA. Moreover, inulin serves a dual purpose as a spray protective agent and a regulator of intestinal flora. Therefore, it was incorporated into INB/IND nanosuspensions for subsequent spray drying, resulting in the preparation of INB/IND nanocrystals (INB/IND-NC). The mucus penetration of INB/IND-NC was 24.30 times that of the control group. Besides, INB/IND-NC exhibited enhanced cellular uptake properties proximately twice that of Raw INB/IND. Importantly, INB/IND-NC exhibited improved therapeutic efficacy in DSS-induced mice by regulating the expression of cytokines, regulating immune responses via downregulating the expression of macrophages, neutrophils, and dendritic cells and maintaining intestinal flora homeostasis. Our study provides a new perspective for applying natural products for treating inflammatory diseases.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Hyaluronic Acid; Indigo Carmine; Inulin; Mice; Mice, Inbred C57BL; Nanoparticles

Isochlorogenic acid A (ICGA-A) is a dicaffeoylquinic acid widely found in various medicinal plants or vegetables, such as Lonicerae japonicae Flos and chicory, and multiple properties of ICGA-A have been reported. However, the therapeutic effect of ICGA-A on colitis is not clear, and thus were investigated in our present study, as well as the underlying mechanisms. Here we found that ICGA-A alleviated clinical symptoms of dextran sodium sulfate (DSS) induced colitis model mice, including disease activity index (DAI) and histological damage. In addition, DSS-induced inflammation was significantly attenuated in mice given ICGA-A supplementation. ICGA-A reduced the fraction of neutrophils in peripheral blood and the infiltration of neutrophils and macrophages in colon tissue, and reduced pro-inflammatory cytokine production and tight junctions in mouse models. Furthermore, ICGA-A down-regulated expression of STAT3 and up-regulated the protein level of IκBα. Our in vitro studies confirmed that ICGA-A inhibited the mRNA expression of pro-inflammatory cytokines. ICGA-A blocked the phosphorylation of STAT3, p65, and IκBα, suppressed the expression STAT3 and p65. In addition, the present study also demonstrated that ICGA-A had no obvious toxicity on normal cells and organs. Taken together, we conclude that ICGA-A mitigates experimental ulcerative colitis (UC) at least in part by inhibiting the STAT3/NF-кB signaling pathways. Hence, ICGA-A may be a promising and effective drug for treating UC.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Mice; Mice, Inbred C57BL; NF-kappa B; NF-KappaB Inhibitor alpha

Indigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.. This open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.. Ten of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.. IN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.. NCT02442960.

Topics: Animals; Colitis; Colitis, Ulcerative; Cytochrome P-450 CYP1A1; Humans; Indigo Carmine; Indigofera; Mice; Quality of Life; RNA

Indigo naturalis (IN) is a traditional Chinese medicine, named Qing-Dai, which is extracted from indigo plants and has been used to treat patients with inflammatory bowel disease (IBD) in China and Japan. Though there are notable effects of IN on colitis, the mechanisms remain elusive. Regarding the significance of alterations of intestinal flora related to IBD and the poor water solubility of the blue IN powder, we predicted that the protective action of IN on colitis may occur through modifying gut microbiota. To investigate the relationships of IN, colitis, and gut microbiomes, a dextran sulfate sodium (DSS)-induced mice colitis model was tested to explore the protective effects of IN on macroscopic colitis symptoms, the histopathological structure, inflammation cytokines, and gut microbiota, and their potential functions. Sulfasalazine (SASP) was used as the positive control. Firstly, because it was a mixture, the main chemical compositions of indigo and indirubin in IN were detected by ultra-performance liquid chromatography (UPLC). The clinical activity score (CAS), hematoxylin and eosin (H&E) staining results, and enzyme-linked immunosorbent assay (ELISA) results in this study showed that IN greatly improved the health conditions of the tested colitis mice, ameliorated the histopathological structure of the colon tissue, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines. The results of 16S rDNA sequences analysis with the Illumina MiSeq platform showed that IN could modulate the balance of gut microbiota, especially by down-regulating the relative quantity of

Topics: Animals; Biopsy; Colitis; Cytokines; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Immunohistochemistry; Indigo Carmine; Inflammation Mediators; Intestinal Mucosa; Metagenomics; Mice; Molecular Structure; RNA, Ribosomal, 16S

Topics: Colitis; Humans; Indigo Carmine; Phlebitis

Indigo naturalis (IND) is an herbal medicine that has been used as an anti-inflammatory agent to treat diseases including dermatitis and inflammatory bowel disease in China. However, the mechanism by which IND exerts its immunomodulatory effect is not well understood.. A murine model of dermatitis and inflammatory bowel disease, both induced by oxazolone (OXA), was treated with IND. The severity of dermatitis was evaluated based on ear thickness measurements and histological scoring. The severity of colitis was evaluated by measuring body weight, histological scoring, and endoscopic scoring. The expression of inflammatory cytokines in ear and colon tissue was evaluated using real-time PCR. 16S rRNA DNA sequencing of feces from OXA-induced colitis mice was performed before and after IND treatment. The effects of IND on OXA-induced colitis were also evaluated after depleting the gut flora with antibiotics to test whether alteration of the gut flora by IND influenced the course of intestinal inflammation in this model.. IND treatment ameliorated OXA dermatitis with a reduction in IL-4 and eosinophil recruitment. However, OXA colitis was significantly aggravated in spite of a reduction in intestinal IL-13, a pivotal cytokine in the induction of the colitis. It was found that IND dramatically altered the gut flora and IND no longer exacerbated colitis when colitis was induced after gut flora depletion.. Our data suggest that IND could modify the inflammatory immune response in multiple ways, either directly (i.e., modification of the allergic immune cell activity) or indirectly (i.e., alteration of commensal compositions).

Topics: Adjuvants, Immunologic; Animals; Colitis; Colon; Dermatitis, Allergic Contact; DNA, Bacterial; Feces; Gastrointestinal Microbiome; Indigo Carmine; Interleukin-13; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Oxazolone; Phytotherapy; Skin

Indigo Naturalis (IN) is used as a traditional herbal medicine for ulcerative colitis (UC). However, the mechanisms of action of IN have not been clarified. We aimed to evaluate the efficacy of IN for ameliorating colonic inflammation. We further investigated the mechanisms of action of IN.. Colitis severity was assessed in dextran sodium sulfate-induced colitis and trinitrobenzene sulfonic acid-induced colitis models with or without the oral administration of IN or indigo, which is a known major component of IN. Colonic lamina propria (LP) mononuclear cells isolated from IN-treated mice were analyzed with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry. LP and splenic mononuclear cells cultured in vitro with IN or indigo were also analyzed. The role of the candidate receptor for indigo, the aryl hydrocarbon receptor (AhR), was analyzed using Ahr-deficient mice.. Colitis severity was significantly ameliorated in the IN and indigo treatment groups compared with the control group. The mRNA expression levels of interleukin (Il)-10 and Il-22 in the LP lymphocytes were increased by IN treatment. The treatment of splenocytes with IN or indigo increased the expression of anti-inflammatory cytokines and resulted in the expansion of IL-10-producing CD4. IN and indigo ameliorated murine colitis through AhR signaling activation, suggesting that AhR could be a promising therapeutic target for UC.

Topics: Animals; CD3 Complex; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cells, Cultured; Colitis; Dextran Sulfate; Drugs, Chinese Herbal; Female; Forkhead Transcription Factors; Gene Expression; Indigo Carmine; Interleukin-10; Interleukin-2 Receptor alpha Subunit; Interleukin-22; Interleukins; Intestinal Mucosa; Leukocytes, Mononuclear; Mice, Knockout; Nuclear Receptor Subfamily 1, Group F, Member 3; Receptors, Aryl Hydrocarbon; RNA, Messenger; Severity of Illness Index; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory; Trinitrobenzenesulfonic Acid

Topics: Colitis; Colonic Polyps; Colonoscopy; Female; Humans; Indigo Carmine; Injections; Methylene Blue; Middle Aged

Topics: Adult; Animals; Colitis; Colon; Drugs, Chinese Herbal; Female; Humans; Indigo Carmine; Indoles; Male; Middle Aged; Phytotherapy; Psoriasis; Rats; Rats, Sprague-Dawley

Topics: Colitis; Colonoscopy; Coloring Agents; Humans; Indigo Carmine