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Background: Mesalamine produces many side effects through oral route such as stomach cramps, throat irritation, back ache and muscle pain. Furthermore, it failed to yield maximum drug release and also not able to produce the drug release for over a period of time at the target site. To overcome these disadvantages, the current research proposed to develop microspheres with pH-dependent bio-resorbable polymers to obtain site-specific controlled drug release at the target site. Materials and Methods: Microspheres were prepared by two methods as ionic gelation and solvent evaporation methods using copolymers such as Eudragit S 100 and PLGA. Results: The prepared formulations were characterized for multiple parameters and the particle size ranges were found in between 5.52 to12.56 µm whereas percentage entrapment efficiency was found in the range of 32 to 98% respectively. Apart from other formulations, PLGA microspheres showed the maximum cumulative percentage drug release through in vitro and ex vivo and the results were found as 96±0.1% and 90.8±0.8% respectively. As compared to Pentasa®, PLGA microspheres showed two folds increase in drug release. The PLGA biodegradability was observed as maximum in the caecal content than other formulations. Conclusion: Compared to Pentasa®, the prepared PLGA microspheres showed the best results and the obtained result was verified with a p-value which is shown <0.005. Based on the results, it was concluded that the prepared PLGA microspheres showed better-controlled drug release than other test formulations. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report describes the clinical course of a 64‐year‐old male with intermittent abdominal pain attributed to recurrent ulcers at the appendiceal orifice. Initial investigations in November 2019 revealed chronic gastritis and ulcers at the appendiceal orifice, prompting consideration of ulcerative colitis (UC). The patient responded well to mesalazine therapy, experiencing relief from symptoms and improved colonoscopy findings in May 2020. Despite discontinuing medication, a recurrence of symptoms in August 2021 led to a repeat colonoscopy showing renewed ulcers. Mesalazine was reinstated, resulting in symptom resolution and improved colonoscopy findings by December 2021. However, in May 2023, a subsequent recurrence of abdominal pain and colonoscopy‐confirmed mucosal changes at the appendiceal orifice prompted reintroduction of mesalazine. The patient remains under regular monitoring on mesalazine therapy. This case highlights the challenges in managing recurrent appendiceal ulcers and the importance of long‐term therapeutic vigilance in suspected UC cases. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprising ulcerative colitis and Crohn's disease is a chronic immune-mediated disease which affects the gastrointestinal tract with a relapsing and remitting course, causing lifelong morbidity. IBD pathogenesis is determined by multiple factors including genetics, immune and microbial factors, and environmental factors. Although therapy options are expanding, remission rates are unsatisfiable, and together with the disease course, response to therapy remains unpredictable. Therefore, the identification of biomarkers that are predictive for the disease course and response to therapy is a significant challenge. Extrachromosomal circular DNA (eccDNA) fragments exist in all tissue tested so far. These fragments, ranging in length from a few hundreds of base pairs to mega base pairs, have recently gained more interest due to technological advances. Until now, eccDNA has mainly been studied in relation to cancer due to its ability to act as an amplification site for oncogenes and drug resistance genes. However, eccDNA could also play an important role in inflammation, expressed both locally in the- involved tissue and at distant sites. Here, we review the current evidence on the molecular mechanisms of eccDNA and its role in inflammation and IBD. Additionally, the potential of eccDNA as a tissue or plasma marker for disease severity and/or response to therapy is evaluated. [ABSTRACT FROM AUTHOR]

Gastrointestinal mucormycosis, a rare fatal fungal infection in an immunocompromised host, affects mainly the stomach. Colonic mucormycosis is infrequent and is associated with high mortality. Perianal involvement is seen in almost one-third of patients with Crohn's disease. Perianal Crohn's disease is a particularly debilitating form of the disease, which requires multidisciplinary care. It may also require profound immunosuppression with biological agents to control disease activity. Opportunistic infections can complicate the disease course in these patients. We present a case of a middle-aged female with perianal Crohn's disease on adalimumab who developed colonic mucormycosis causing a flare in her disease activity. This patient highlights the need to increase awareness about fungal infections as a cause of disease flare in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

A key challenge for the effective treatment of intestinal diseases, including inflammatory bowel disease (IBD), is to develop an oral drug delivery system that can resist gastric acid erosion and efficiently release drugs after rapid entry into the intestine. In the present work, we developed oral composite nanoparticles (MSZ@PRHS) consisting of a rough mesoporous silica (RHS) loaded with Mesalazine (MSZ) and a CAP polymer membrane for targeted relief of inflammation in colitis. At the pH values of the simulated stomach and small intestine, the release rate of MSZ from MSZ@PRHS was low, while at the pH values of the simulated colon, the release rate of MSZ was high. In dextran sulfate sodium salt (DSS)-induced acute colitis mouse model, compared with oral administration of the drug Mesalazine in the equivalent solution form, oral administration of PRHS loaded with drug-loaded nanoparticles can significantly alleviate the symptoms of inflammatory bowel disease, and improve the therapeutic effect. We propose that the intestinal microenvironment provides an interface for nanocomposites switch and a promising drug delivery platform for the management and treatment of many intestinal diseases, where controlled drug release and prolonged residence time are required. [ABSTRACT FROM AUTHOR]

The oral delivery strategy of natural anti-oxidant and anti-inflammatory agents has attracted great attention to improve the effectiveness of ulcerative colitis (UC) treatment. Herein, we developed a novel orally deliverable nanoparticle, carboxymethyl chitosan (CMC)-modified astaxanthin (AXT)-loaded nanoparticles (CMC-AXT-NPs), for UC treatment. The CMC-AXT-NPs were evaluated by appearance, morphology, particle size, ζ-potential, and encapsulation efficiency (EE). The results showed that CMC-AXT-NPs were nearly spherical in shape with a particle size of 34.5 nm and ζ-potential of −30.8 mV, and the EE of CMC-AXT-NPs was as high as 95.03%. The CMC-AXT-NPs exhibited preferable storage stability over time and well-controlled drug-release properties in simulated intestinal fluid. Additionally, in vitro studies revealed that CMC-AXT-NPs remarkably inhibited cytotoxicity induced by LPS and demonstrated superior antioxidant and anti-inflammatory abilities in Raw264.7 cells. Furthermore, CMC-AXT-NPs effectively alleviated clinical symptoms of colitis induced by dextran sulfate sodium salt (DSS), including maintaining body weight, inhibiting colon shortening, and reducing fecal bleeding. Importantly, CMC-AXT-NPs suppressed the expression of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β and ameliorated DSS-induced oxidative damage. Our results demonstrated the potential of CMC-modified nanoparticles as an oral delivery system and suggested these novel AXT nanoparticles could be a promising strategy for UC treatment. [ABSTRACT FROM AUTHOR]

Objective: To investigate effects of mesalazine (MS) on proliferation, apoptosis and inflammatory injury of cell model of ulcerative colitis (UC) induced by lipopolysaccharide (LPS), as well as transforming growth factor-β1 (TGF-β)/Smad signaling pathway effect in this study. Methods: Human colonic epithelial cells NCM-460 cultured in vitro were induced UC model by LPS, and divided into Con group (no treatment, LPS group (l mg/L LPS, MS group (0.1, 0.2, 0.4 mg/L MS+1 mg/L LPS) and inhibitor group (10 µmol/L TGF-β1/Smad signaling pathway inhibitor LY2109761+0.2 mg/L MS+1 mg/L LPS). Cell morphology, proliferation, apoptosis and levels of inflammatory factors and TGF-β1/Smad pathway-related markers were examined by inverted microscope, EdU assay, Hoechst 33258 staining, ELISA and Western blot. Results: LPS treatment highly induced cell proliferation rate and Smad7 protein level compared with Con group, while apoptotic cells, inflammatory factors TNF-α and IL-6, soluble interleukin-2 receptor (sIL-2R) release, as well as TGF-β1, p-Smad2, p-Smad3 protein expressions were increased; the above effects induced by LPS was reversed by MS in a dose-dependent manner (P<0.05). Compared with 0.2 mg/L MS group, NCM-460 cells proliferation rate and Smad7 expression were increased, while apoptotic cells, TNF-α and IL-6, sIL-2R releases, and TGF-β1, p-Smad2, p-Smad3 protein expressions were decreased (P<0.05). Conclusion: MS can attenuate LPS-induced apoptosis and inflammatory injury in NCM-460 cells, and this protection was possibly through suppressing TGF-β1/Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs. [ABSTRACT FROM AUTHOR]

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457–485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a relapsing and remitting condition that requires continuous treatment to reduce the risk of relapse. Alongside genetic factors, diet and lifestyle factors are heavily implicated in the pathogenesis of the disease, with diets high in meat and ultra-processed foods and low in fibre-rich plant foods thought to be central to the disease process. There is considerable interest in using dietary interventions to prevent, treat and IBD, with the hope that this can limit and, in some cases, even eliminate the use of pharmaceutical interventions. A whole food plant-based diet (WFPBD) is an attractive option given its emphasis on foods that promote gut health and reduce inflammation and the avoidance of foods that are associated with dysbiosis and inflammation. Here we describe 3 case histories of patients with ulcerative colitis and the successful use of a WFPBD for remission induction and maintenance with over 2 years of follow-up. [ABSTRACT FROM AUTHOR]

Mesalazine is an established and recommended first-line treatment for mild-to-moderate ulcerative colitis (UC). For patients with moderately active UC, the choice to use mesalazine or to initiate treatment with an oral corticosteroid or anti-tumor necrosis factor (TNF) agent is not clearly informed from current guidelines. The use of mesalazine is supported by robust clinical evidence supporting its efficacy at inducing remission in patients with moderately active disease. A key advantage of mesalazine is its tolerability profile being similar to that of placebo, which contrasts with that of the corticosteroids and advanced therapies, where there is the potential for significant toxicities. Mesalazine also has cost advantages over anti-TNFs and other advanced therapies. Evidence supports the consideration of all patients with moderately active UC for first-line mesalazine therapy at an optimized dose of ≥4g/d (± 1g/d rectal). Patients responding to treatment within 2 weeks should continue at ≥4g/d for at least 6 months before a dose reduction is considered, since this then alters the pattern of disease.

Beeswax is selected as a natural coating material for the development of new colon specific drug delivery systems charged by mesalamine. In a first step, beeswax microparticles are prepared using hot-melt process of microencapsulation where drug:beeswax ratio, stirring speed, emulsifier concentration and pH of external phase are varied for the optimization of the drug entrapment and microparticles’ morphology. The effect of the nature of the emulsifier is also discussed by studying the hydrophilic–lipophilic balance (HLB) value. In a second step, to obtain delayed delivery systems, bi-layered microspheres are elaborated by the process of emulsion–solvent evaporation using ethylcellulose or cellulose acetate butyrate as outer enteric coating layer. All formulations are characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy and optical microscopy. The drug release is established in simulated gastric, small bowel and colon liquids and the release mechanism is discussed by applying the Korsmeyer–Peppas model.

Background and aims5-aminosalicylates (5-ASA) are frequently used in the management of Crohn's disease (CD). We used a de-identified administrative claims database to compare patterns and outcomes of continuing versus stopping 5-ASA in patients with CD who escalated to anti-metabolite monotherapy.MethodsPatients with CD on 5-ASA who were new users of anti-metabolite monotherapy and followed for at least 12 months from OptumLabs® Data Warehouse. Three patterns of 5-ASA use were identified: stopped 5-ASA, short-term 5-ASA (use for  6 months after starting anti-metabolites). Outcomes (need for corticosteroids, risk of CD-related hospitalization and/or surgery, treatment escalation to biologic therapy) were compared using Cox proportional hazard analysis adjusting for key covariates, with a 12-month immortal time period.ResultsOf 3036 patients with CD who were new-users of anti-metabolite monotherapy, 667 (21.9%), 626 (20.6%), and 1743 (57.4%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of corticosteroid use (HR, 1.24 [1.08-1.42]), without an increase in risk of CD-related hospitalization (HR, 1.21 [0.98-1.49]), CD-related surgery (HR, 1.28 [0.90-1.80]) or treatment escalation (HR, 0.85 [0.62-1.20]). Sensitivity analyses using a 3-month window after initiation of anti-metabolites to classify patients as continuing vs. stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded.Conclusion5-ASAs are frequently continued long-term even after escalation to anti-metabolite therapy in patients with CD but offer no clinical benefit over stopping 5-ASA.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease of the gastrointestinal tract. This study aimed to determine the effect of cathelicidinrelated antimicrobial peptide (Cramp) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice and to investigate the underlying mechanisms. Acute UC was induced in C57BL/6 mice with 3% DSS for 7 days, 4 mg/kg b.w. synthetic Cramp peptide was administrated once daily starting on day 4 of the experimental period. Mice were evaluated for body weight, colon length, colon histopathology, and inflammatory cytokines in colon tissue. Using 16 s rRNA sequencing, the composition structure of gut microbiota was characterized. Metabolomic profiling of the serum was performed. The results showed that DSS treatment significantly induced intestinal damage as reflected by disease activity index, histopathological features, and colon length, while Cramp treatment significantly prevented these trends. Meanwhile, Cramp treatment decreased the levels of inflammatory cytokines in both serum and colonic tissue on DSS-induced colitis. It was also observed that DSS damaged the integrity of the intestinal epithelial barrier, whereas Cramp also played a protective role by attenuating these deteriorated effects. Furthermore, Cramp treatment reversed the oxidative stress by increasing the antioxidant enzymes of GSH-PX and decreasing the oxidant content of MDA. Notably, compared to the DSS group, Cramp treatment significantly elevated the abundance of Verrucomicrobiota at the phylum level. Furthermore, at the genus level, Parasutterella and Mucispirllum abundance was increased significantly in response to Cramp treatment, although Roseburia and Enterorhabdus reduced remarkably. Metabolic pathway analysis of serum metabolomics showed that Cramp intervention can regulate various metabolic pathways such as α-linolenic acid, taurine and hypotaurine, sphingolipid, and arachidonic acid metabolism. The study concluded that Cramp significantly ameliorated DSS-induced colonic injury, colonic inflammation, and intestinal barrier dysfunction in mice. The underlying mechanism is closely related to the metabolic alterations derived from gut microbiota. [ABSTRACT FROM AUTHOR]

Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate (5AS, mesalamine, mesalazine) is used in the treatment of ulcerative colitis (UC) and other inflammatory bowel diseases (IBD). PAS, a structural analog of pABA, is biosynthetically incorporated by bacterial dihydropteroate synthase (DHPS), ultimately yielding a dihydrofolate (DHF) analog containing an additional hydroxyl group in the pABA ring: 2'-hydroxy-7,8-dihydrofolate. It has been reported to perturb folate metabolism in M. tuberculosis, and to selectively target M. tuberculosis dihydrofolate reductase (mtDHFR). Studies of PAS metabolism are reviewed, and possible mechanisms for its mtDHFR inhibition are considered. Although 5AS is a more distant structural relative of pABA, multiple lines of evidence suggest a related role as a pABA antagonist that inhibits bacterial folate biosynthesis. Structural data support the likelihood that 5AS is recognized by the DHPS pABA binding site, and its effects probably range from blocking pABA binding to formation of a dead-end dihydropterin-5AS adduct. These studies suggest that mesalamine acts as a gut bacteria-directed antifolate, that selectively targets faster growing, more folate-dependent species. [ABSTRACT FROM AUTHOR]

Personalised medicine and the identification of predictors of the efficacy of specific drugs represent the ultimate goal for the treatment of ulcerative colitis (UC) in order to break the current therapeutic ceiling. JAK inhibitors are a new class of advanced therapies, orally administered, showing a good profile of efficacy and safety in both randomised controlled trials (RCTs) and real-world studies. Unfortunately, to date, it is not possible to draw the ideal profile of a patient maximally benefiting from this class of drugs to guide clinicians' therapeutic choices. Baseline clinical activities and inflammatory biomarkers, as well as their early variation after treatment initiation, emerged as the main predictors of efficacy from post hoc analyses of RCTs with tofacitinib. Similar findings were also observed in the real-life studies including mainly patients with a history of pluri-refractoriness to biological therapies. At last, a few new biomarkers have been explored, even though they have not been validated in large cohorts. This paper provides a review of the current knowledge on clinical variables and biomarkers predicting response to JAK inhibitors in UC. [ABSTRACT FROM AUTHOR]

The primary aim of this study is to create a targeted drug delivery system for Mesalamine, specifically aimed at the colon. Nine different formulations of Mesalamine tablets were developed using a combination of microbial degradation polymers such as Inulin, Locust bean gum, and Xanthan gum, along with MCC, PVPK30, magnesium stearate, and talc through the direct compression method. Various parameters including hardness, weight variation, drug content uniformity, friability, and in vitro drug release were evaluated for all the prepared tablets. FTIR studies indicated the absence of interactions between the drug and polymers. Among the formulations, F9 demonstrated the highest in vitro drug release of 96.25% over 12 hours, thus establishing it as the optimized formulation. [ABSTRACT FROM AUTHOR]

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148). [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic inflammatory disorder of the intestinal mucosa and a prevalent gastrointestinal condition in developed countries. Peiminine, derived from the Fritillaria imperialis plant, exhibits remarkable anti-inflammatory and anti-cancer properties. This study aims to investigate the anti-inflammatory effects of peiminine in an experimental model of ulcerative colitis. Ulcerative colitis was induced intra-rectally in all groups, except the negative control, using 100 μl of 4% acetic acid. Peiminine treatment was initiated after ulcerative colitis induction and symptom manifestation. After the final injection, mice were sacrificed on day 15 for assessment. Various parameters were evaluated, including disease activity index, myeloperoxidase activity, nitric oxide levels, production and expression of IL-1, IL-6, TNF-α cytokines, and expression of IL-1β, IL-6, TNF-α, iNOS, and COX2 genes. Microscopic pathological evaluation was performed on colon tissue. Peiminine treatment resulted in reduced levels of NO, MPO, IL-1β, IL-6, and TNF-α. Furthermore, the expression of IL-1β, IL-6, TNF-α genes, iNOS, and COX2 genes was decreased in response to peiminine treatment in these mice. This study demonstrates the effectiveness of peiminine in alleviating inflammatory manifestations and mitigating intestinal tissue damage in an experimental model of ulcerative colitis, probably by anti-inflammatory procedure. Peiminine holds potential as a therapeutic adjunct for the management of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is an intestinal inflammatory condition characterized by a rise in inflammatory mediator production and oxidative stress. Topiramate is an anticonvulsant agent with effectiveness on a wide range of seizures, which is anti-oxidative. This study aims to examine the protective effects of topiramate on acetic acid-induced ulcerative colitis in rats. Rats were randomly divided into four groups as follows: control, acetic acid, acetic acid + topiramate, and acetic acid + dexamethasone groups. Topiramate (100 mg/kg/day) or dexamethasone (2 mg/kg/day) was administered for six consecutive days, and ulcerative colitis was induced on the first day of the study by transrectal administration of 4% acetic acid. Four hours after the last dose of treatments, animals of each group were sacrificed, and colon tissues were removed for further macroscopic, histopathologic, and biochemical analyses. Treatment with topiramate markedly decreased colonic lesions and macroscopic scores as well as the improvement of histopathologic changes. Topiramate also effectively decreased the levels of malondialdehyde and upregulated the activity of anti-oxidative enzymes, including catalase, superoxide dismutase, and glutathione peroxidase. Our results reveal that the administration of topiramate ameliorates acetic acid-induced colitis in rats via anti-oxidative properties, and further studies may introduce it as an effective therapeutic candidate to decrease ulcerative colitis severity. [ABSTRACT FROM AUTHOR]

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods to generate race-specific efficacy estimates. Then, we tested the effect modification by race by comparing the race-specific estimates derived from independent evidence syntheses. We computed ratios of relative risks (RRRs) and performed tests of statistical interaction. We analyzed data from five randomized, placebo-controlled trials evaluating IFX as induction and maintenance therapy for adults with moderate-to-severe UC (875 participants; 45% Asians). We found no substantial evidence of racial differences concerning the efficacy of IFX in inducing clinical response (RRR = 0.89, 95% CI: 0.66–1.20; p = 0.44), clinical remission (RRR = 0.58, 95% CI: 0.24–1.44; p = 0.24), and mucosal healing (RRR = 0.99, 95% CI: 0.69–1.41; p = 0.95), or maintaining clinical remission (RRR = 0.81, 95% CI: 0.46–1.42; p = 0.45) and mucosal healing (RRR = 0.84, 95% CI: 0.48–1.46; p = 0.53), between Asian and Caucasian populations. Future clinical studies should expand the participation of racial minorities to comprehensively assess potential racial differences in the effectiveness of advanced therapies, including IFX, in the context of treating UC. [ABSTRACT FROM AUTHOR]

Background: Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD. Despite the huge therapeutic progress of the last decade, one must not forget about the side effects that currently available medications might have and the challenges to both patient and physician. Case presentation: We present the case of a 33-year-old woman, that initially was admitted for diffuse abdominal pain, nausea and bloating. After careful investigation she was diagnosed with a drug induced acute pancreatitis, caused by sulfamethoxazole/trimethoprim taken for UTI. Further investigations established a diagnosis of ulcerative colitis. Initial treatment with mesalamine resulted in another acute pancreatitis event that required hospitalization. An anti-TNF therapy with infliximab was started with initial clinical remission but then she developed another adverse reaction, this time paradoxical psoriasis, while having an IBD flare. So, this begged the question, how do we treat a patient that had an adverse reaction to every prior treatment? Conclusion: Developing newer and newer therapies will bring also different possible adverse events that should be carefully diagnosed and managed. [ABSTRACT FROM AUTHOR]

The main objective of this study was to formulate mesalamine loaded alginate microspheres for local treatment of ulcerative colitis and optimized batch were then filled in capsules coated with Eudragit S 100. The microspheres were prepared by ionic gelation method. Box Behnken design using design expert software was employed in formulating and optimizing the microspheres. Microspheres were evaluated for particle size, shape and entrapment efficiency. The optimized batch was then filled in capsule coated with Eudragit S100.This encapsulated system released alginate microspheres at colon region in a sustained manner. The drug release of microspheres showed a longer residence time in the colon due to better mucoadhesion properties of sodium ALG. Therefore mesalamine-loaded alginate microspheres enteric coated in capsules can be potential delivery system for local treatment of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Mesalamine, also called 5-ASA (5-aminosalicylic acid), is a largely used anti-inflammatory agent and is a main choice to treat Ulcerative Colitis. This report is aimed to investigate enzymatic processes involved in the oxidation of mesalamine to better understand some of its side-effects. Oxidation with oxygen (catalyzed by ceruloplasmin) or with hydrogen peroxide (catalyzed by peroxidase or hemoglobin) showed that these oxidases, despite their different mechanisms of oxidation, could recognize mesalamine as a substrate and trigger its oxidation to a corresponding quinone-imine. These enzymes were chosen because they may recognize hydroquinone (a p-diphenol) as substrate and oxidize it to p-benzoquinone and that mesalamine, as a p-aminophenol, presents some similarities with hydroquinone. The UV-Vis kinetics, FTIR and 1H NMR supported the hypothesis of oxidizing mesalamine. Furthermore, mass spectrometry suggested the quinone–imine as reaction product. Without enzymes, the oxidation process was very slow (days and weeks), but it was markedly accelerated with the oxidases, particularly with peroxidase. Cyclic voltammetry supported the hypothesis of the oxidative process and allowed a ranking of susceptibility to oxidizing mesalamine in comparison with other oxidizable drug molecules with related structures. The susceptibility to oxidation was higher for mesalamine, in comparison with Tylenol (acetaminophen) and with aspirin (salicylic acid). [ABSTRACT FROM AUTHOR]

Abstract Objectives Segmental colitis associated with diverticulosis (SCAD) has close endoscopic and pathological similarities to ulcerative colitis (UC) and Crohn's disease. Clinical data on SCAD are limited in Japan. We examined the endoscopic and clinicopathological features of patients with SCAD. Methods This single‐center retrospective study included 13 patients with SCAD between 2012 and 2022. Endoscopic findings were categorized as follows: type A (swollen red patches 5–10 mm at the top of mucosal folds), mild and moderate type B (mild‐to‐moderate UC‐like findings), type C (aphthous ulcers resembling Crohn's disease), and type D (severe UC‐like findings). Results Overall, six, five, and two patients were diagnosed with type A, mild type B, and moderate type B disease, respectively. Among the type A cases, two spontaneously progressed to moderate type B and one escalated to type D, necessitating an emergency sigmoidectomy owing to perforation peritonitis, despite repeated antibiotic treatments. Histopathologically, diffuse neutrophil and lymphocyte infiltration with cryptitis were noted in all type A cases, whereas UC‐like alterations were observed in type B and D cases. Seven type B cases were treated with oral 5‐aminosalicylic acid and/or salazosulfapyridine. Clinical remission was achieved in three mild type B cases and one moderate type B case, while clinical relapse and remission were noted in three moderate type B cases. No anti‐inflammatory treatment was required in three type A and two mild type B cases. Conclusions Aggressive anti‐inflammatory treatment should be considered for SCAD with UC‐like findings due to the potential risk of severe ulceration, stenosis, and/or perforation.

BackgroundAcute intermittent porphyria (AIP) is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population. AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase (PBGD) activity. Acute attacks are provoked by stressors such as certain medications, alcohol, and infection. We herein present the first case report of AIP detected in a post-renal transplant patient.Case summaryThe patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephro-pathy. He subsequently developed diabetes mellitus which required insulin therapy. He had been treated in the recent past with local mesalamine for proctitis. He presented with classic but common symptoms of AIP including intense abdominal pain, hypertension, and anxiety. He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained. His urinary postprandial blood glucose level was 60 mg/24 h (normal, < 2 mg/24 h). He was placed on a high carbohydrate diet, and his symptoms slowly improved.ConclusionThis case report describes a common presentation of an uncommon disease, in which post-transplant complications and medications may have contributed to precipitating the previously undiagnosed AIP. We hypothesize that the low-carbohydrate diet and insulin with which our patient was treated may have led to the attacks of AIP. Alternatively, our patient's mesalamine treatment for proctitis may have led to an acute AIP crisis. A high index of suspicion is needed to consider the diagnosis of a heme synthesis disorder, which presents with the common symptoms of abdominal pain, high blood pressure, and anxiety.

Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn's disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0–1.0 using a shake-flask technique at 293.2–313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van't Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively. [ABSTRACT FROM AUTHOR]

Background: Inflammation and oxidative activities within the gut play major roles in the pathogenesis of ulcerative colitis (UC). We aimed to determine the effect of Melissa officinalis, an antioxidant and anti-inflammatory agent, on the colon histological characteristics in acetic acid (AA)-induced UC in rat models. Methods: Thirty-six male rats with AA-induced colitis were divided into 5 groups: no treatment (AA); daily treatment with 300 mg/kg Melissa officinalis orally (MO) and rectally (MR); and 100 mg/kg mesalamine orally (AO) and rectally (AR). Macroscopic and histopathological evaluation of the colon, along with a biochemical laboratory evaluation, were performed 10 days after UC induction. Results: All treatment groups demonstrated lower macroscopic grading scores compared to the AA group. After treatment with MO, 42.9% of cases demonstrated no macroscopic changes, while 14.3% demonstrated only mucosal erythema. In the MR group 28.6% of rats had no changes in their mucosal lining and 28.6% had only mucosal erythema. Following histopathological evaluation, the AO group had lower scores regarding the severity of ulcer, inflammation, destruction, crypt abscess, and disorganization compared to the MO group. (P=0.02) The MR group demonstrated lower microscopic scores compared to the MO group, and also lower macroscopic scores compared to the AR group, although not significantly (P>0.05). Conclusions: Both oral and topical administration of Melissa officinalis have satisfactory healing properties compared to mesalamine, with topical route having better Results:. Therefore, further studies are needed to establish the benefit of Melissa officinalis administration (both orally and topically) within a UC treatment protocol. [ABSTRACT FROM AUTHOR]

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels (Ictidomys tridecemlineatus). We fed active yearling ground squirrels a diet containing the gut-specific nonsteroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 wk. Mesalazine treatment had slight effects on microbial community diversity in the cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased proinflammatory and increased antiinflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected, and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species. NEW & NOTEWORTHY Adiposity and obesity are caused, at least in part, by inflammation of metabolic tissues. Hibernators, like ground squirrels, undergo this same metabolic inflammation during their summer fattening period. We attempted to curb this inflammation, and thus fattening, using mesalazine. We found that mesalazine did curb the inflammation but did not affect fattening, likely due to the strong drive to fatten in hibernators. [ABSTRACT FROM AUTHOR]

Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1β, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1β, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential. Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated. [ABSTRACT FROM AUTHOR]

An exploration was conducted on the potential therapeutic properties of dandelion polysaccharide (DP) in addressing 3% dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in murine models. Subsequent assessments focused on DP's influence on inflammation, oxidative stress, and ferroptosis in IEC-6 cells damaged by H2O2. Results highlighted the efficacy of DP in mitigating weight loss, improving disease activity index scores, normalizing colon length, and alleviating histological abnormalities in the affected mice. DP repaired colonic mitochondrial damage by enhancing iron transport and inhibited iron death in colonic cells. Moreover, DP played a pivotal role in enhancing the antioxidant potential. This was evident from the increased expression levels of Nrf2, HO-1, NQO-1, and GSH, coupled with a decrease in MDA and 4-HNE markers in the UC-afflicted mice. Concurrently, DP manifested inhibitory effects on MPO activation and transcription levels of inflammatory mediators such as IL-1β, IL-6, TNF-α, and iNOS. An upsurge in the expression of occludin and ZO-1 was also observed. Restoration of intestinal tightness resulted in decreased serum LPS and LDH levels. Thereafter, administration of DP by gavage increased fecal flora diversity and relative abundance of probiotics in UC mice. Analysis of metabolites indicated that DP counteracted metabolic disturbances and augmented the levels of short-chain fatty acids in ulcerative colitis-affected mice. In vitro studies underscored the role of DP in triggering Nrf2 activation, which in turn exhibited anti-inflammatory, antioxidant, and anti-ferroptotic properties. Summarily, DP's capacity to activate Nrf2 contributes to the suppression of ferroptotic processes in intestinal epithelial cells of UC-affected mice, enhancing the intestinal barrier's integrity. Beyond that, DP possesses the ability to modulate the gut microbiome, rectify metabolic imbalances, rejuvenate short-chain fatty acid levels, and bolster the intestinal barrier as a therapeutic approach to UC. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon. Incidence is on the rise in India. Therapeutic arsenal has evolved in the last two decades. European Crohn's and Colitis Organisation guidelines are used to plan the treatment of the patients. In this article, we review the current and emerging management of UC according to disease severity based on Indian publications. [ABSTRACT FROM AUTHOR]

Grapefruit is commonly consumed around the world due to its nutritional and medicinal properties. Ulcerative colitis (UC) accounts for an inflammatory bowel disease (IBD) accompanied by irritation, recurrent inflammation, and ulceration of the colon's mucosa. Our objective was to assess the antiinflammatory and antioxidant impacts of grapefruit juice (GFJ) in rat with UC induced by acetic acid (AA). There were five groups made up of 35 mature male rats. Group 2 served as a positive control with UC, whereas group 1 was preserved as a negative control. For 8 weeks, groups 3, 4, and 5 received UC while also given 2.5, 5 or 10% of GFJ orally. Feed efficiency ratio (FER), body weight growth (BWG), and feed intake (FI) were computed. From rat eye orbital plexuses blood samples were taken to separate the serum after centrifugation. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were assessed utilizing serum samples. The antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in serum were quantified. Serum inflammatory cytokines as tumor necrosis factor alpha (TNFα), interleukin 1 β (IL1 β), IL6 and IL8, as well as triglycerides (TG) and total cholesterol (TC) were measured. In liver homogenate, glutathione (GSH) and malondialdehyde (MDA) were determined. Additionally, histopathology of the colon was accomplished. Our findings specified that GFJ at 10% significantly decreased FI, BWG and FER, cytokines TNFα, IL1 β, IL6 and IL8 and TC and TG. Relative to the positive controls, the rats treated with GFJ exhibited elevated serum concentrations of SOD, GPx, and CAT enzymes. Liver GSH was elevated and MDA was reduced. Histopathological examination of the colon showed that GFJ at 10% reduced ulcerative colitis. Because grapefruit juice has strong antiinflammatory and antioxidant characteristics and reduces oxidative stress and inflammation in rats, grapefruit juice, at a concentration of 10%, likely protects against ulcerative colitis. Patients with ulcerative colitis may find it helpful to consume grapefruit juice as a beverage. [ABSTRACT FROM AUTHOR]

Background: Ferroptosis, a type of programmed cell death triggered by oxidative stress, was suspected to play a role in ulcerative colitis. Indigo naturalis is highly effective against ulcerative colitis, but its mechanism is unclear. This study found that indigo naturalis treatment suppressed ferroptosis. Methods: We analyzed 770 mRNA expressions of patients with ulcerative colitis. Suppression of ferroptosis by indigo naturalis treatment was shown using a cell death assay. Malondialdehyde levels and reactive oxygen species were analyzed in CaCo-2 cells treated with indigo naturalis. Glutathione metabolism was shown by metabolomic analysis. Extraction of the ingredients indigo naturalis from the rectal mucosa was performed using liquid chromatograph—mass spectrometry. Results: Gene expression profiling showed that indigo naturalis treatment increased antioxidant genes in the mucosa of patients with ulcerative colitis. In vitro analysis showed that nuclear factor erythroid-2-related factor 2-related antioxidant gene expression was upregulated by indigo naturalis. Indigo naturalis treatment rendered cells resistant to ferroptosis. Metabolomic analysis suggested that an increase in reduced glutathione by indigo naturalis. The protein expression of CYP1A1 and GPX4 was increased in the rectum by treatment with indigo naturalis. The main ingredients of indigo naturalis, indirubin and indigo inhibited ferroptosis. Indirubin was detected in the rectal mucosa of patients with ulcerative colitis who were treated with indigo naturalis. Conclusions: Suppression of ferroptosis by indigo naturalis in the intestinal epithelium could be therapeutic target for ulcerative colitis. The main active ingredient of indigo naturalis may be indirubin. [ABSTRACT FROM AUTHOR]

Objectives: Myocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post‐MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post‐MI therapy, as distinct antifibrotic effects have recently been demonstrated. Methods: At 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR. Results: Compared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression. Conclusions: Our findings warrant further studies on mesalazine as a potential add‐on therapy post‐MI, as perivascular fibrosis development was successfully prevented. [ABSTRACT FROM AUTHOR]

Two straightforward, fast, easy, accurate, and sensitive spectrophotometric methods were developed to measure mesalazine either in its pure form or in tablet dosage form The proposed procedures, specifically, rely on a condensation reaction between mesalazine and aromatic aldehydes, (method A) and (method B), to produce yellow color Schiff's bases. For methods A and B, the concentration ranges where Beer's relationship was observed were 0.4-10 μg mL-1 with a limit of detection of 0.1070 μg mL-1 and a limit of quantification of 0.1323 μg mL-1, and 2-15 μg mL-1 with a limit of detection of 0.3244 μg mL-1 and 0.4010 μg mL-1, respectively. The recovery percentage was 97.82% to 102.1% and 98.15% to 99.91% for the two proposed methods. The proposed methods have been used successfully to determine mesalazine in their tablet formulations. [ABSTRACT FROM AUTHOR]