The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.
Animals ; Mice ; Caspase 1/genetics* ; Colitis, Ulcerative/genetics* ; Colon ; Dextran Sulfate/adverse effects* ; Disease Models, Animal ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Mesalamine/pharmacology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Scutellaria baicalensis/chemistry* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology*

This study deciphered the mechanism of Shenling Baizhu Powder in treatment of mouse model of ulcerative colitis(UC) via NOD-like receptor thermoprotein domain 3(NLRP3) signaling pathway. After three days of adaptive feeding, 70 SPF-grade BALB/c mice were randomized into 7 groups: normal group, model group(dextran sodium sulfate, DSS), mesalazine group(DSS + 5-aminosalicylic acid, 5-ASA), NLRP3 inhibitor group(DSS + MCC950), and high-, medium-, and low-dose Shenling Baizhu Powder groups(DSS + high-, medium-, and low-dose Shenling Baizhu Powder), with 10 mice per group. The normal group had free access to double distilled water, and the remaining groups had free access to DSS-containing water to establish the acute UC model. Intragastric administration was started at the same time as modeling for one week. During the experiment, the general mental state and disease activity of each group of mice were recorded and scored. After the experiment, colon and serum samples were collected. The pathological changes in colon tissue were observed through hematoxylin-eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin-18(IL-18) and myeloperoxidase(MPO) in colon tissue and interleukin-1β(IL-1β) in serum. Immunofluorescence(IF) and immunohistochemistry(IHC) methods were employed to examine the expression of NLRP3 and IL-18 in colon tissue. Western blot was employed to measure the protein levels of NLRP3, apoptosis-associated speck-like protein(ASC), cystein-aspartate protease 1(caspase-1), and downstream inflammatory cytokines in colon tissue. Compared with the normal group, the modeling of UC increased the disease activity index(DAI), colon pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue(P<0.05, P<0.01). Furthermore, the modeling caused obvious pathological changes and up-regulated the expression of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.01). Compared with the model group, the administration of corresponding drugs decreased the DAI, pathological injury score, IL-1β level in serum, and IL-18 and MPO levels in colon tissue, and down-regulated the protein levels of NLRP3, caspase-1, ASC, pro-IL-1β, cleaved-IL-1β, pro-IL-18, and cleaved-IL-18 in the colon(P<0.05, P<0.01). According to the results of previous study and this study, we concluded that Shenling Baizhu Powder can alleviate the inflammatory response and intestinal damage of DSS-induced UC by regulating the expression of the proteins and inflammatory cytokines associated with NLRP3 signaling pathway.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Dextran Sulfate/adverse effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-18/genetics* ; Powders ; Colon/metabolism* ; Caspase 1 ; Mesalamine/adverse effects* ; Mice, Inbred BALB C ; Disease Models, Animal ; Cytokines/metabolism* ; Water ; Colitis/pathology*

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.
Animals ; Colitis/drug therapy* ; Mesalamine/pharmacology* ; Mice ; Nitroreductases ; Oleanolic Acid/pharmacology* ; Prodrugs

BACKGROUND/AIMS: Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. METHODS: UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. RESULTS: A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). CONCLUSIONS: CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.
Colitis, Ulcerative ; Drug Compounding ; Humans ; Medication Adherence ; Mesalamine ; Patient Acceptance of Health Care ; Patient Compliance ; Prospective Studies ; Recurrence ; Tablets ; Ulcer ; Visual Analog Scale

Mesalazine suppositories are widely used to treat ulcerative colitis and have a guaranteed safety profile, but although rare, they can cause pulmonary toxicity. A 35-year-old woman with ulcerative colitis was diagnosed to have acute eosinophilic pneumonia after 29 days of oral mesalazine use and improved after mesalazine and corticosteroid were withdrawn. Reintroduction of mesalazine suppositories resulted in acute eosinophilic pneumonia recurrence after 28 days. Mesalazine re-administration (even via a different route) in patients with a history of mesalazine-induced eosinophilic pneumonia should be undertaken cautiously, because eosinophilic pneumonia may recurrence.
Adult ; Colitis, Ulcerative ; Eosinophils ; Female ; Humans ; Mesalamine ; Pulmonary Eosinophilia ; Recurrence ; Suppositories ; Ulcer

BACKGROUND/AIMS: A once-daily (OD) regimen of 5-aminosalicylic acid (5-ASA) was easier to comply with than a divided daily (DD) regimen, and that treatment efficacy for ulcerative colitis (UC) was not affected by the dosing regimen. This study evaluated treatment adherence of OD and DD dosing in the Korean UC patients. METHODS: This study was a prospective, multicenter, randomized trial. UC patients were enrolled who have been in remission for more than 3 months. Patients were randomly assigned to the OD or DD group in a 1:1 ratio. The primary endpoint was adherence rate measured by tablet counts and self-reported adherence rate at 3, 6, 9, and 12 months. The relapse rate was measured at 1 year. RESULTS: Data from the 180 patients who were randomized were analyzed. Both self-reported adherence rate and adherence rate measured by tablet counts were not different at every points, including 1 year. The patients' satisfaction of the OD group was higher than that of the DD group (P<0.001). At 1 year, 91.2% and 95.5% of patients in the OD group and DD group had maintained clinical remission, respectively (P=0.37). CONCLUSIONS: The adherence rates were not different between the OD group and DD group. The patients' satisfaction was higher in the OD group than in the DD group. 5-ASA OD dosing might have the same effect as DD for the maintenance of UC remission.
Colitis, Ulcerative ; Humans ; Inflammatory Bowel Diseases ; Mesalamine ; Prospective Studies ; Recurrence ; Treatment Outcome ; Ulcer

BACKGROUND/AIMS: A recent study revealed increasing incidence and prevalence of inflammatory bowel disease (IBD) in Iran. The Iranian Registry of Crohn's and Colitis (IRCC) was designed recently to answer the needs. We reported the design, methods of data collection, and aims of IRCC in this paper. METHODS: IRCC is a multicenter prospective registry, which is established with collaboration of more than 100 gastroenterologists from different provinces of Iran. Minimum data set for IRCC was defined according to an international consensus on standard set of outcomes for IBD. A pilot feasibility study was performed on 553 IBD patients with a web-based questionnaire. The reliability of questionnaire evaluated by Cronbach's α. RESULTS: All sections of questionnaire had Cronbach's α of more than 0.6. In pilot study, 312 of participants (56.4%) were male and mean age was 38 years (standard deviation=12.8) and 378 patients (68.35%) had ulcerative colitis, 303 subjects (54,7%) had college education and 358 patients (64.74%) were of Fars ethnicity. We found that 68 (12.3%), 44 (7.9%), and 13 (2.3%) of participants were smokers, hookah and opium users, respectively. History of appendectomy was reported in 58 of patients (10.48%). The most common medication was 5-aminosalicylate (94.39%). CONCLUSIONS: To the best of our knowledge, IRCC is the first national IBD registry in the Middle East and could become a reliable infrastructure for national and international research on IBD. IRCC will improve the quality of care of IBD patients and provide national information for policy makers to better plan for controlling IBD in Iran.
Administrative Personnel ; Appendectomy ; Colitis ; Colitis, Ulcerative ; Consensus ; Cooperative Behavior ; Data Collection ; Dataset ; Education ; Feasibility Studies ; Humans ; Incidence ; Inflammatory Bowel Diseases ; Iran ; Male ; Mesalamine ; Middle East ; Opium ; Pilot Projects ; Prevalence ; Prospective Studies

BACKGROUNDS: Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD) increased prevalence and economic burden. OBJECTIVES: This study aimed to investigate drug use pattern in IBD patients in a real world. METHODS: National Health Insurance claim data from 2010 to 2014 were used in this population-based study. All IBD patients diagnosed during study period were enrolled. IBD medications included 5-aminosalicylic acid (ASA), glucocorticoid, immunomodulator and anti-tumor necrosis factor-α agent(anti TNF-α). Growth rate of IBD prevalence, prescribed drug classes, duration of drug therapy and medication cost were analyzed. Number and percentage of patients for categorical variables, and mean and median for continuous variables were presented. RESULTS: Total numbers of patients were 131,158 and 57,286 during 5 years, and their annual growth rate were 3.2 and 5.7% for UC and CD. UC and CD were prevalent in the 40–50 (41.2%) and 20–30 age groups (36.0%). About 60% of IBD patients was prescribed any of medications. 5-ASA was the most frequently prescribed, followed by corticosteroid and immunomodulator. Anti TNF-α use was the lowest, but 5 times higher than UC in CD. Combination therapies with different class of drugs were in 29% for UC and 62% for CD. Mean prescription days per patient per year were 306 and 378, and the median medication cost per patient per year was KRW 420,000 (USD 383) and KRW 830,000 (USD755), for UC and CD, respectively. CONCLUSIONS: Increasing prevalence of IBD requires further studies to contribute to achieve better clinical outcomes of drug therapy.
Colitis, Ulcerative ; Crohn Disease ; Drug Therapy ; Health Expenditures ; Humans ; Inflammatory Bowel Diseases ; Mesalamine ; National Health Programs ; Necrosis ; Prescriptions ; Prevalence

Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.
Colitis* ; Colitis, Ulcerative* ; Colonoscopy ; Diagnosis ; Fever ; Humans ; Hypersensitivity ; Inflammatory Bowel Diseases ; Medical Records ; Mesalamine* ; Phenotype ; Ulcer*

Symptomatic ulcerative colitis (UC) can be a chronic, disabling condition. Flares in disease activity are associated with many of the negative impacts of mild-to-moderate UC. Rapid resolution of flares can provide benefits to patients and healthcare systems. i Support Therapy–Access to Rapid Treatment (iSTART) introduces patient-centered care for mild-to-moderate UC. iSTART provides patients with the ability to self-assess symptomology and self-start a short course of second-line treatment when necessary. An international panel of experts produced consensus statements and recommendations. These were informed by evidence from systematic reviews on the epidemiology, mesalazine (5-ASA) treatment, and patient use criteria for second-line therapy in UC. Optimized 5-ASA is the first-line treatment in all clinical guidelines, but may not be sufficient to induce remission in all patients. Corticosteroids should be prescribed as second-line therapy when needed, with budesonide MMX® being a preferred steroid option. Active involvement of suitable patients in management of UC flares has the potential to improve therapy, with patients able to show good accuracy for flare self-assessment using validated tools. There is a place in the UC treatment pathway for an approach such as iSTART, which has the potential to provide patient, clinical and economic benefits.
Adrenal Cortex Hormones ; Budesonide ; Colitis, Ulcerative* ; Consensus* ; Delivery of Health Care ; Epidemiology ; Humans ; Mesalamine ; Patient-Centered Care ; Self-Assessment ; Ulcer*