Effective Treatment For Ulcerative Colitis Research Articles

Walnut peptide ameliorates DSS-induced colitis in mice by inhibiting inflammation and modulating gut microbiota

The incidence of ulcerative colitis (UC) is increasing each year, and its course is characterized by alternating remission-relapse; currently, there is no effective treatment for UC. Peptides produced from the hydrolysis of walnut proteins have physiological functions such as anti-inflammatory and antioxidant properties. The aim of this study was to analyze the preventive effect of walnut polypeptide (WP) on UC and to preliminarily screen bioactive peptides in WP. The results of in vitro experiments showed that WP was able to alleviate the LPS-induced inflammatory response by inhibiting M1 polarization in Raw 264.7 cells and thereby alleviating the LPS-induced inflammatory response. The results of in vivo experiments showed that dietary supplementation with 500 mg/kg WP significantly alleviated dextran sodium sulfate (DSS)-induced weight loss, colon shortening, and elevated DAI scores. WP treatment was able to suppress DSS-induced inflammatory responses in mice by inhibiting macrophage M1 polarization and NF-κB signaling pathway. WP intervention also helped maintain intestinal barrier integrity by promoting tight junction protein expression and mucus secretion. In addition, 16S rDNA sequencing showed that WP ameliorated gut microbial disorder induced by DSS, as evidenced by a decrease in the abundance of harmful bacteria (Erysipelatoclostridium, Helicobacter, and Parasutterella) and an increase in the abundance of beneficial bacteria (Flavonifractor, Anaerotignum, and Alistipes) after WP intervention. In conclusion, this study demonstrates that WP ameliorates DSS-induced colonic inflammation in mice by inhibiting inflammation, modulating the gut microbiota and repairing the intestinal barrier.

Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota

Ethnopharmacological relevanceChinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration. Aim of the studyThis study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17 cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice. Materials and methods61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.96 and 11.83 g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1β, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-Iβ, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome. ResultsGQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17 cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1β, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1β. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function. ConclusionsGQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17 cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.

Resveratrol-loaded pH-responsive Mesona chinensis polysaccharides-zein nanoparticles for effective treatment of ulcerative colitis.

Resveratrol (Res) is promising food functional factor with favorable antioxidant and anti-inflammatory properties, although its poor water solubility and low bioavailability limit extensive application. Therefore, in combination with another promising polysaccharide (Mesona chinensis polysaccharides, MCP), Res-loaded food nanocarriers (ResNPs) were developed to increase its water solubility, bioactivity and targeting properties. ResNPs were then applied to alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis. Resveratrol can be well encapsulated in MCP-based nanoparticles in an amorphous state, improving its water solubility. ResNPs showed pH-response controlled release behavior in the gastrointestinal tract and increased the enrichment of Res in the colon. In vivo experiments of ResNPs against DSS-induced ulcerative colitis (UC) revealed that ResNPs significantly improved UC symptoms, modulated intestinal inflammation and down-regulated oxidative stress levels compared to free Res. ResNPs also play an positive role with respect to inhibiting the mitogen-activated protein kinase pathway and promoting the expression of tight junction proteins. In addition, ResNPs improved the species composition and relative abundance of intestinal flora in UC mice, which effectively regulated the balance of intestinal flora and promoted the production of short-chain fatty acids. These results suggest that MCP-based nanoparticles can effectively improve the solubility of resveratrol and enhance its in vivo bioactivity. Moreover, the present study also provides a new strategy for the prevention and treatment of UC with food polyphenol. © 2024 Society of Chemical Industry.

Engraftment of essential functions through multiple fecal microbiota transplants in chronic antibiotic-resistant pouchitis—a case study using metatranscriptomics

BackgroundIleal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). Around 50% of patients will experience pouchitis, an idiopathic inflammatory condition. Antibiotics are the backbone of treatment of pouchitis; however, antibiotic-resistant pouchitis develops in 5–10% of those patients. It has been shown that fecal microbiota transplantation (FMT) is an effective treatment for UC, but results for FMT antibiotic-resistant pouchitis are inconsistent.MethodsTo uncover which metabolic activities were transferred to the recipients during FMT and helped the remission, we performed a longitudinal case study of the gut metatranscriptomes from three patients and their donors. The patients were treated by two to three FMTs, and stool samples were analyzed for up to 140 days.ResultsReduced expression in pouchitis patients compared to healthy donors was observed for genes involved in biosynthesis of amino acids, cofactors, and B vitamins. An independent metatranscriptome dataset of UC patients showed a similar result. Other functions including biosynthesis of butyrate, metabolism of bile acids, and tryptophan were also much lower expressed in pouchitis. After FMT, these activities transiently increased, and the overall metatranscriptome profiles closely mirrored those of the respective donors with notable fluctuations during the subsequent weeks. The levels of the clinical marker fecal calprotectin were concordant with the metatranscriptome data. Faecalibacterium prausnitzii represented the most active species contributing to butyrate synthesis via the acetyl-CoA pathway. Remission occurred after the last FMT in all patients and was characterized by a microbiota activity profile distinct from donors in two of the patients.ConclusionsOur study demonstrates the clear but short-lived activity engraftment of donor microbiota, particularly the butyrate biosynthesis after each FMT. The data suggest that FMT triggers shifts in the activity of patient microbiota towards health which need to be repeated to reach critical thresholds. As a case study, these insights warrant cautious interpretation, and validation in larger cohorts is necessary for generalized applications. In the long run, probiotics with high taxonomic diversity consisting of well characterized strains could replace FMT to avoid the costly screening of donors and the risk of transferring unwanted genetic material.1wvY14mjpJT86R5RsB8tdiVideo

Mucoadhesive and thermosensitive Bletilla striata polysaccharide/chitosan hydrogel loaded nanoparticles for rectal drug delivery in ulcerative colitis

Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and β-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.

The Underlying Changes in Serum Metabolic Profiles and Efficacy Prediction in Patients with Extensive Ulcerative Colitis Undergoing Fecal Microbiota Transplantation.

(1) Background: Fecal microbiota transplantation (FMT) is an effective treatment for ulcerative colitis (UC). Metabolomic techniques would assist physicians in clinical decision-making. (2) Methods: Patients with active UC undergoing FMT were enrolled in the study and monitored for 3 months. We explored short-term changes in the serum metabolic signatures of groups and the association between baseline serum metabolomic profiles and patient outcomes. (3) Results: Forty-four eligible patients were included in the analysis. Of them, 50.0% and 29.5% achieved clinical response and clinical remission, respectively, 3 months post-FMT. The top two significantly altered pathways in the response group were vitamin B6 metabolism and aminoacyl-tRNA biosynthesis. Both the remission and response groups exhibited an altered and enriched pathway for the biosynthesis of primary bile acid. We found a clear separation between the remission and non-remission groups at baseline, characterized by the higher levels of glycerophosphocholines, glycerophospholipids, and glycerophosphoethanolamines in the remission group. A random forest (RF) classifier was constructed with 20 metabolic markers selected by the Boruta method to predict clinical remission 3 months post-FMT, with an area under the curve of 0.963. (4) Conclusions: FMT effectively induced a response in patients with active UC, with metabolites partially improving post-FMT in the responsive group. A promising role of serum metabolites in the non-invasive prediction of FMT efficacy for UC demonstrated the value of metabolome-informed FMT in managing UC.

Ileo-Anal Pouch Anastomosis and New Remedial Approaches for Ulcerative Colitis: A Review Article.

Ulcerative colitis (UC)causes diffusefriability and superficial wall degeneration that is accompanied by bleeding. UC, now recognized as a global illness, affects millions of people globally. The most effective treatment for UC is Ileal Pouch Anal Anastomosis (IPAA). Many medical experts and patients favor proctocolectomy with IPAA because it improves bowel function and allows feces to pass via the anus.Considering the most recent research, systematic reviews, statistical analysis, and recommendations, a selective literature search was carried out. The database used was PubMed. The current work provides a summary of surgical alternatives, results, and pre-and postoperative treatment for UC patients. In the course of their illness, about 30% of UC patients will need surgery. Due to its natural limitation to the colon and rectum, UC may mostly be treated surgically. The preferred surgical process is a restorative proctocolectomy with an IPAA. A 30% postoperative complication rate and a 0.1% death rate for this operation are both shown in large studies. One of the biggest things preventing UC from being successfully treated surgically is pouchitis. A long-run success rate of the pouch is>90% after 10follow-ups, despite a significant surgical complication rate. For patients with UC to have the best possible outcome, extensive collaboration among the various specialties in the pre and postoperative context is crucial. In skilled centers, more than 90%of the total patients can eventually achieve a decent quality of life despite a 30% likelihood of early postoperative problems. UC patients may be cured with proctocolectomy, but there is a risk of morbidity that must be considered, especially in pediatric patients. As a result of advancements in our comprehension of the pathogenic mechanisms causing UC, new therapies have been proposed, the most significant change being the emergence of anti-tumor necrosis factor (TNF) medications.

Efficacy and Safety of Sulfasalazine Suspension in Children With Ulcerative Colitis.

Sulfasalazine (SZ) is commonly used to treat pediatric ulcerative colitis (UC). SZ can be compounded into a suspension form which is beneficial for children with difficulty swallowing a pill. Despite being utilized for over 40 years, there is a lack of published data on the efficacy and safety of SZ suspension in children with UC. Recently, third-party payors have begun refusing to pay for SZ suspension due to lack of data. In this retrospective study, we reviewed the electronic medical records of patients ages <18 years diagnosed with UC from June 1999 to December 2019 at Boston Children's Hospital and treated with SZ suspension as a first-line agent. We obtained demographics, clinical, and endoscopic data to measure outcomes at 1 year and long term. Of 57 patients treated with SZ suspension, 52 (91%) had a follow-up and 26 of 52 (50%) remained in steroid-free remission at 1 year. Two patients were switched to SZ tablets due to nonmedical reasons and 11 (21%) required rescue treatment (2 infliximab, 1 tacrolimus, 8 6-mercaptopurine/azathioprine) within a year. Three required colectomy within a year and 5 in long term. Four (8%) developed nonserious adverse reactions and switched to 5-aminosalicylates (5-ASA) by 1 year. The median duration of long-term follow-up was 36 months (range, 2-205 months) with 28 requiring treatment escalation in long term. SZ suspension is a safe and effective treatment for UC in children with difficulty swallowing a pill. The 1-year remission rate on this treatment is comparable to 5-ASA utilized in children.

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

Huazhuojiedu decoction (HZJDD), a traditional Chinese medicine prescription, has been clinically proven to be an effective treatment for ulcerative colitis (UC). However, the mechanism of HZJDD in the treatment of UC remains unclear. This study combined network pharmacology with experimental validation to explore the potential mechanism of HZJDD on UC. First, the relationship network diagrams between HZJDD and UC were established based on multiple databases. Then, the HZJDD-UC intersection genes target network was constructed and Gene Ontology-Biological processes (GO-BP) analysis was performed to discover the potential pharmacological mechanism. Finally, the results of GO-BP were verified in dextran sulfate sodium salt (DSS) induced UC rats. The network pharmacology results showed that 119 active components and 146 potential targets were screened for HZJDD, and six of the top 15 biological processes belonged to inflammatory response, cellular response to hypoxia, and cellular response to lipopolysaccharide (LPS). The GO-BP results indicated that the mechanism of HZJDD treatment of UC was related to inflammation, oxidative stress, and the regulation of LPS. Animal experiments showed that HZJDD could significantly reduce the disease activity index (DAI) score, improve colon length, and effectively repair the histomorphological and micromorphological changes in DSS-induced UC rats. Moreover, HZJDD reduced the expressions of CRP, TNF-α, IL-6, LPS, IL-1β, and IL-18; downregulated the activity of MDA; and upregulated the activities of CAT, GSH, and SOD in DSS-induced UC rats. Furthermore, HZJDD suppressed the expression of the NLRP3/caspase-1 signaling pathway at the gene and protein levels to inhibit pyroptosis. Network pharmacology and animal experiments showed that HZJDD exerted a therapeutic effect on DSS-induced UC rats by reducing inflammation, oxidative stress, and restraining the NLRP3/caspase-1 signaling pathway to inhibit pyroptosis.

Renshen Baidu powder protects ulcerative colitis via inhibiting the PI3K/Akt/NF-κB signaling pathway.

Ulcerative colitis is a chronic and relapsing inflammatory bowel disease without satisfactory therapy available recently. Renshen Baidu powder (RSBDP) is a classic Chinese medicinal formula used since Chinese Song dynasty and has been proven as an effective treatment of ulcerative colitis in clinics. However, the active ingredients and the molecular mechanism have not been fully disclosed. It is imperative to explore the active ingredients and the mechanism of RSBDP. In this study, the potential active components for ulcerative colitis treatment in RSBDP were determined and predicted in silicon, and its molecular mechanisms were also presented, in which the PI3K/Akt/NF-κB signaling pathway was recognized to be vital. Basically, the pharmacodynamics and mechanistic studies of RSBDP for ulcerative colitis were implemented on TNBS-induced experimental rats. The results showed that RSBDP could ameliorate the disease activity index and colon weight, as well as improve colonic shortening and colon histology. In addition, the tumor necrosis factor-α (TNF-α), diamine oxidase, intercellular adhesion molecule-1, and endotoxin in serum were also reduced. It is worth mentioning that the PI3K/Akt/NF-κB signaling pathway was inhibited after RSBDP administration via inhibiting the phosphorylation of proteins. In conclusion, RSBDP effectively ameliorates TNBS-induced colitis rats by inhibiting the PI3K/Akt/NF-κB signaling pathway.

Pharmacokinetic and gut microbiota analyses revealed the effect of Lactobacillus acidophilus on the metabolism of Olsalazine in ulcerative colitis rats

Olsalazine is a typical 5-aminosalicylic acid (5-ASA) drug that depends on gut microbiota to liberate its anti-inflammatory moiety 5-ASA in the treatment of ulcerative colitis (UC). In recent decades, 5-ASA drugs combined with probiotics have achieved a better effective treatment for UC. Mechanisms of combination therapy have been widely discussed from a pharmacodynamic perspective. However, it is still unclear whether the better therapeutic efficacy of combination therapy was made by changing the metabolism of 5-ASA drugs in the colon under the regulation of probiotics. In the present study, combined with pharmacokinetic and gut microbiota analyses, we systematically evaluated the potential effect of Lactobacillus acidophilus (L. acidophilus) on the metabolism of Olsalazine at three levels (pharmacokinetic characteristics, metabolic microbiota, and metabolic enzymes) to offer some insights into this issue. As pharmacokinetic results showed, L. acidophilus barely had an influence on the pharmacokinetic parameters of Olsalazine, 5-ASA, and N-Ac-5-ASA. Notably, the colonic exposure of 5-ASA was not affected by L. acidophilus. Gut microbiota results also illustrated that L. acidophilus did not change the total abundance of azoreductase (azoR) and N-acetyltransferase (NAT) associated gut microbiota and enzymes, which are involved in the metabolism of Olsalazine. Both pharmacokinetic and gut microbiota results revealed that L. acidophilus did not increase the colonic exposure of 5-ASA to improve the efficacy of combination therapy. L. acidophilus played its role in UC treatment by regulating gut microbiota composition and amino acid, phenolic acid, oligosaccharide, and peptidoglycan metabolic pathways. There was no potential medication risk of combination therapy of Olsalazine and L. acidophilus. In summary, this research provided strong evidence of medication safety and a comprehensive understanding of therapeutic advantages for combination therapy of probiotics and 5-ASA drugs from the pharmacokinetic and gut microbiota perspectives.

PH-sensitive liposomes for colonic co-delivery of mesalazine and curcumin for the treatment of ulcerative colitis

The ineffectiveness of the current management of ulcerative colitis (UC) demands novel pharmaceutical techniques and advance therapeutic strategies to facilitate safe and efficacious treatment of the disease. In this quest, mesalazine (MZ), a 5-aminosalicylate with anti-inflammatory and potent antioxidant activities, along with curcumin (CM), a natural anti-inflammatory and antioxidant polyphenol, were found to produce a synergistic efficacy to efficiently alleviate UC. In the present study, we have formulated pH-sensitive liposomes (LS) containing a low-dose combination of MZ and CM as a potential therapy for UC. It was hypothesized that the synergistic action of the two drugs, pH-dependent colon-specific delivery, and use of LS as a nano-technological drug carrier system could diminish drug-associated side effects, reduce the dose and provide effective treatment strategy for UC. The guinea pig model of UC was used to evaluate the in vivo efficacy of pH sensitive MZ-CM co-loaded LS and found to be more efficacious than single-drug LS or drug solution. Furthermore, both drugs exhibited high antioxidant activity and mitigated the oxidative stress present along UC; resulting in an effective treatment of UC. In conclusion, eudragit-S100 coated MZ-CM liposomes is a promising treatment strategy for the effective oral therapy of UC.

Orally Deliverable Dual-Targeted Pellets for the Synergistic Treatment of Ulcerative Colitis.

PurposeThe effective treatment of ulcerative colitis (UC) poses substantial challenges, and the aetiopathogenesis of UC is closely related to infectious, immunological and environmental factors. Currently, there is a considerable need for the development of orally bioavailable dosage forms that enable the effective delivery of therapeutic drugs to local diseased lesions in the gastrointestinal tract.MethodsBerberine (BBR) and Atractylodes macrocephala Koidz (AM) volatile oil, derived from the Chinese herbs Coptis chinensis Franch and Atractylodes macrocephala Koidz, have anti-inflammatory and immunomodulatory activities. In this study, we prepared colon-targeted pellets loaded with BBR and stomach-targeted pellets loaded with AM volatile oil for the synergistic treatment of UC. The Box–Behnken design and β-cyclodextrin inclusion technique were used to optimize the enteric coating formula and prepare volatile oil inclusion compounds.ResultsThe two types of pellets were spherical and had satisfactory physical properties. The pharmacokinetic results showed that the AUC and MRT values of the dual-targeted (DPs) pellets were higher than those of the control pellets. In addition, in vivo animal imaging confirmed that the DPs could effectively deliver BBR to the colon. Moreover, compared with sulfasalazine and monotherapy, DPs exerted a more significant anti-inflammatory effect by inhibiting the expression of inflammatory factors including IL-1β, IL-4, IL-6, TNF-α and MPO both in serum and tissues and enhancing immunity by decreasing the production of IgA and IgG.ConclusionThe DPs play a synergistic anti-UC effect by exerting systemic and local anti-inflammatory and provide an effective oral targeted preparation for the treatment of UC.

Glycogen-based pH and redox sensitive nanoparticles with ginsenoside Rh2 for effective treatment of ulcerative colitis

The purpose of this study is to construct a pH and redox sensitive nanoparticle to effectively deliver ginsenoside Rh2 for the treatment of ulcerative colitis (UC). Herein, glycogen was modified by urocanic acid and α-lipoic acid (α-LA) to obtain an amphiphilic polymer (LA-UaGly). Such polymer LA-UaGly could self-assemble to form nanoparticles (Blank NPs) in water with excellent stability, which could also successfully encapsulated ginsenoside Rh2 to form Rh2 nanoparticles (Rh2 NPs) with encapsulation efficiency of 74.36 ± 0.34%. DLS analysis indicated Rh2 NPs were spherical with a particle size of 128.9 ± 0.3 nm. As expected, Rh2 NPs exhibited typical pH and redox dual response release behaviour as well as the excellent in vivo safety. In vitro tests showed that Rh2 NPs could effectively internalize and release Rh2 into RAW264.7 cells, and protect cells from apoptosis (p < 0.05). More interestingly, Rh2 NPs exhibited strong anti-inflammatory activity via significantly inhibiting the overproduction of nitric oxide (NO) and inflammatory cytokines (TNF-α, IL-1β and IL-6) (p < 0.05). In vivo experiments suggested that Rh2 NPs significantly ameliorated the weight loss, colon length, disease activity index (DAI) score, and myeloperoxidase (MPO) activity in mice caused by dextran sulfate sodium salt (DSS) (p < 0.05). Simultaneously, pathological analysis proved that Rh2 NPs could significantly reduce histological damage and inflammatory infiltration in mice. Rh2 NPs could also effectively regulate the intestinal flora of mice by improving the species uniformity and abundance of the intestinal flora of mice and restoring the species diversity of the intestinal flora. In addition, both in vivo and in vitro experiments proved that Rh2 NPs had stronger anti-inflammatory activity than Rh2. This study provides a promising strategy for the effective treatment of UC.

Acupuncture for ulcerative colitis: a systematic review and meta-analysis of randomized clinical trials

BackgroundUlcerative colitis, characterized by diarrhea, bloody stools and abdominal pain, is a chronic, idiopathic inflammatory disease of the colonic mucosa. In recent years, the incidence of ulcerative colitis presents an increasing trend year by year. Acupuncture, as a potential effective treatment for ulcerative colitis, is widely used in clinical practice.MethodsWe searched PubMed, the Cochrane Library, Chinese CBM Database, China National Knowledge Infrastructure, Chinese VIP Information, and Wanfang Database from the date of the establishment of each database up to March, 2019. We included randomized controlled clinical trials (RCT) comparing acupuncture versus conventional conventional medicine or comparing acupuncture combined with conventional medicine versus conventional medicine in participants with ulcerative colitis. Two authors screened all references, assessed the risk of bias and extracted data independently. We summarized data using risk ratios (RR) with 95% confidence intervals (CI) for binary outcomes. We performed meta-analyses using random effects model. We assessed overall quality of evidence using GRADE.ResultsWe included 13 RCTs (1030 participants, 515 in the acupuncture group and 515 in the control group). Only one study tested head acupuncture, and the other 12 tested body acupuncture. The treatment duration ranged from 14 to 60 days. Seven trials compared acupuncture alone versus conventional medicine, and six compared acupuncture combined with conventional medicine versus conventional medicine. Acupuncture combined with mesalazine showed better clinical effect (improved clinical symptoms, colonoscopy results and stool examination results) (RR 1.25, 95% CI 1.19 to 1.41; 232 participants; 4 trials; low quality evidence) and better colonoscopy curative effect (RR 1.33, 95% CI 1.04 to 1.71; 108 participants; 2 trials; moderate quality evidence) compared to mesalazine. Acupuncture showed better clinical effect compared to the combination of metronidazole and sulfasalazine (RR 1.21, 95%CI 1.10, 1.34; 318 participants; 3 trials; moderate quality evidence). There was no significant difference in the incidence of adverse events between groups.ConclusionsBoth acupuncture alone and acupuncture combined with conventional medicine may be effective in treating ulcerative colitis compared to conventional medicine. Our findings must be interpreted with caution due to high or unclear risk of bias of the included trials.

Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis

The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and −16.3 ± 1.54 mV and AgNPs loaded with MES (AgNPs-MES) was 101 ± 9 nm and −14.27 ± 2.16 mV. The dissolution study revealed about 54% drug release after 5 h indicating release of drug at the colonic site. The in vivo study was carried out on acetic acid induced ulcerative colitis rats and efficacy of treatment was assessed through evaluation of disease activity index and level of antioxidants as well as tumor necrosis factor-α after 7th and 14th day of induction of colitis. Histopathological evaluation of colonic tissue was also carried out. The results revealed that AgNPs-MES (high dose) provided better therapeutic efficacy for the treatment of UC as compared to its low dose, MES alone, MES-MAP, AgNPs alone and MAP alone. It was concluded that MAP based AgNPs loaded with MES were successfully formulated and found to be effective in treating ulcerative colitis.

Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry.

SummaryBackgroundTofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC).AimTo evaluate effectiveness, safety and use of tofacitinib in daily practice.MethodsUC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid‐free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid‐free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation.ResultsIn total, 123 UC patients (95% anti‐TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12‐26). The proportion of patients in corticosteroid‐free clinical, biochemical, and combined corticosteroid‐free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11‐0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib‐related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9‐26), 18% (95% CI 8‐28) and 21% (95% CI 14‐39) respectively.ConclusionTofacitinib is an effective treatment for UC after anti‐TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.

P424 Economic evaluation of vedolizumab SC for the treatment of moderate-to-severe ulcerative colitis in Canada

Abstract Background Vedolizumab intravenous (IV), a gut selective humanised monoclonal antibody, is indicated for the management of moderately to severely active Ulcerative Colitis (UC) and has been shown in the only head-to-head clinical trial within UC to be superior to adalimumab (NCT02497469). Furthermore, the novel vedolizumab subcutaneous (SC) has recently been proven to be an effective treatment of UC (NCT02611830). The objective of this study is to estimate the comparative cost-effectiveness of vedolizumab IV with updated efficacy data, and vedolizumab SC for the first time. Both vedolizumab IV and SC have been compared with other publicly reimbursed biologics for the treatment of patients with moderate-to-severe UC from a Canadian public healthcare payer perspective. Methods A hybrid decision tree/Markov model was developed to simulate the clinical course of UC, translating the disease course into costs and quality-adjusted life-years (QALYs). Comparative efficacy of vedolizumab SC, vedolizumab IV, adalimumab, infliximab IV, and golimumab were sourced from a network meta-analysis. Drug and disease management costs (2019 $CAD) were sourced from Ontario public payer schedules of benefits. Utilities were sourced from the literature. Clinical and economic outcomes were projected over a lifetime and discounted at 1.5% annually. Results Within a mixed bio-naïve/experienced population, vedolizumab SC resulted in slightly more QALYs than vedolizumab IV and dominated adalimumab (Table 1); vedolizumab SC yielded an incremental cost-effectiveness ratio (ICER) of $CAD 6,727 per QALY and $CAD 52,673 per QALY relative to golimumab and to infliximab (for which the price of a biosimilar was used), respectively. Further scenario analysis within bio-naïve populations supported the robustness of the base-case results, demonstrating that vedolizumab SC or vedolizumab IV were either dominant or cost-effective across all scenarios. Conclusion Our analysis suggests that vedolizumab SC and vedolizumab IV are a cost-effective therapeutic alternative relative to other biologics for moderate-to-severe UC in Canada. Future research will expand the analysis across all biologic comparators as they are used in the real world.

DOP58 Tofacitinib for ulcerative colitis: Results of the ICC Registry, a nationwide prospective observational cohort study

Abstract Background Tofacitinib is a janus kinase 1 and 3 inhibitor approved for the treatment of ulcerative colitis (UC). Real-world evidence is needed to evaluate the effectiveness, usage and safety in daily practice. Methods UC patients in whom tofacitinib was started in 15 hospitals (8 academic, 7 non-academic) participated in the ICC Registry: a Dutch prospective, observational registry. Visits were planned at baseline, Week 12, and 24. Patients with both clinical (Short Clinical Colitis Activity Index (SCCAI) &amp;gt;2) and objective disease activity (endoscopy (Mayo &amp;gt;0), C-reactive protein (CRP) &amp;gt;5 mg/l or faecal calprotectin (FCP) &amp;gt;250 µg/g) were included. In this study, corticosteroid-free clinical remission (SCCAI ≤2), biochemical remission (FCP ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, dose optimisation, and effect on lipids were determined at Week 24. Only patients from centres with routine endoscopic follow-up (regardless of symptoms) were analysed to determine endoscopic remission (Mayo = 0) at Week 12. All analyses were done on an intention-to-treat basis. Results In total, 111 UC patients (95% anti-TNF, 60% vedolizumab, 4% ustekinumab exposed) were followed for a median of 24 weeks (IQR 12–26). All patients had both active clinical and objective disease (SCCAI 8 (IQR 5–11), FCP 1800µg/g (IQR 633–2682)). Corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29%, 25%, and 19%, respectively. Endoscopic remission was achieved in 21% of patients (n = 33) at Week 12. Prior vedolizumab exposure was associated with a lower remission rate at week 24 (OR 0.33, 95% CI 0.11–0.94) in multivariable analysis. In total, 36 patients (88 per 100 patient-years) experienced tofacitinib-related adverse events (most common: cutaneous lesions and headache) of which 6 patients (18 per 100 patient-years) discontinued treatment. No thromboembolic events were reported. We observed 4 cases of herpes zoster re-activation but no severe infections (requiring hospitalisation). During follow-up 14 hospitalisations and 5 (4.5%) colectomies were performed. Cholesterol, HDL, and LDL increased between baseline and week 12 (18% (95% CI 9–26, n = 35), 18% (95% CI 8–28, n = 35) and 27% (95% CI 14–39, n = 35), respectively). At week 24, 33% of patients used 10 mg twice daily. Conclusion Tofacitinib is an effective treatment for UC after anti-TNF and/or vedolizumab failure. We did observe a relatively high rate of adverse events in this refractory UC cohort.