Evaluation of 5 versus 10 granulocyteaphaeresis sessions in steroid-dependent ulcerative colitis: A pilot, prospective, multicenter, randomized study

AIM： To evaluate the efficacy of 5 compared to ：tO granulocyteaphaeresis sessions in patients with active steroid-dependent ulcerative colitis. METHODS： In this pilot, prospective, multicenter randomized trial, 20 patients with moderately active steroid-dependent ulcerative colitis were randomized to 5 or 10 granulocyteaphaeresis sessions. The primary objective was clinical remission at wk 17. Secondary measures included endoscopic remission and steroid consumption.RESULTS： Nine patients were randomized to 5 granulocyteaphaeresis sessions （group 1） and 11 patients to 10 granulocyteaphaeresis sessions （group 2）. At wk 17, 37.5% of patients in group 1 and 45.45% of patients in group 2 were in clinical remission. Clinical remission was accompanied by endoscopic remission in all cases. Eighty-six percent of patients achieving remission were steroid-free at wk 17. Daily steroid requirements were significantly lower in group 2. Eighty-nine per cent of patients remained in remission during a one year follow-up. One serious adverse event, not related to the study therapy, was reported. CONCLUSION： Granulocyteaphaeresis is safe and effective for the treatment of steroid-dependent ulcerative colitis. In this population, increasing the number of aphaeresis sessions is not associated with higher remission rates, but affords a significant steroid-sparing effect.

Efficacy of low-dose thiopurine therapy for the induction of remission in steroid-dependent ulcerative colitis: Comparison with cytapheresis

Background: The role of azathioprine (AZA) and 6-mercaptopurine (6-MP) in the induction of remission in patients with ulcerative colitis (UC) remains unclear. Aims: To compare the efficacy and safety of low-dose thiopurine (AZA/6-MP) and cytapheresis (CAP) for the induction of remission in patients with steroid- dependent UC. Patients and Methods: We reviewed the clinical course of 65 patients with steroid-dependent UC with moderate activity, who were treated with either low-dose AZA/6-MP (T-group, n = 38) or with CAP (C-group, n = 27). The efficacy and safety for the first 10 weeks after the start of the therapies were compared between the two groups. The cumulative probability curves of treatment failure were estimated by the Kaplan-Meier method. Clinical remission was defined as an ulcerative colitis activity index value of less than 150 without any other treatments. Results: Neither clinical characteristics, concomitant therapies, nor laboratory data (except for serum albumin levels) were different between the two groups. The remission rate at 10 weeks was not different between the two groups (55.3% in the T-group and 70.4% in the C-group, p = 0.22 in the intention-to-treat analysis). The frequencies of adverse events did not differ be- tween the two groups (p = 0.12). The cumulative pro- bability of treatment failure at 10 weeks was 44.7% for the T-group and 29.6% for the C-group (p = 0.23). Conclusions: Low-dose thiopurine therapy is an alter- native candidate for the induction of remission in pa- tients with steroid-dependent, moderate UC.

Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.

Ulcerative colitis and bullous pemphigoid:Direct association or a medication side effect:A case report

BACKGROUND Bullous pemphigoid(BP)is an autoimmune blistering skin disorder.It is associated with other autoimmune disorders and the use of certain drugs.We describe a case of BP in a patient with ulcerative colitis(UC)treated with mesalamine.CASE SUMMARY A 38-year-old male patient with UC and a history of multiple flares was maintained on mesalamine with good clinical response.One year after starting mesalamine,he sought medical care following the onset of a severe itchy rash of several weeks’duration with a recent appearance of skin bullae.A biopsy of the skin revealed subepidermal blistering dermatitis with focal eosinophilic spongiosis.Direct immunofluorescence studies revealed linear IgG and C3 immune reactant deposits at the dermoepidermal junction,consistent with the diagnosis of BP.Prednisone therapy alleviated his symptoms.However,tapering prednisone led to re-eruption of the bullae.CONCLUSION BP should be considered when patients with UC develop skin manifestations.Although BP is not one of the extraintestinal manifestations of UC,there may be an association between these two conditions.Whether treatment with mesalamine or other therapeutic agents plays a role in the development of BP remains unclear.

Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis

BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis(UC),including steroid-dependent and steroid-refractory patients,to achieve and maintain steroid-free remission.However,clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient.Cytapheresis(CAP)is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects.This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients.AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients.METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP.We analyzed the following points:(1)Efficacy of the first course of CAP;(2)Efficacy of the second,third,and fourth courses of CAP in patients who experienced relapses during the observation period;(3)Efficacy of CAP in colonic mucosa;and(4)Long-term efficacy of CAP.Clinical efficacy was evaluated using Lichtiger’s clinical activity index or Sutherland index(disease activity index).Mucosal healing was evaluated using Mayo endoscopic subscore.The primary and secondary endpoints were the rate of achievement of steroidfree remission and the rate of sustained steroid-free remission,respectively.Statistical analysis was performed using the paired t-test and chi-squared test.RESULTS The rates of clinical remission,steroid-free remission,and poor effectiveness after CAP were 69.1%,45.5%,and 30.9%,respectively.There were no significant differences in rate of steroid-free remission between patients with steroiddependent and steroid-refractory UC.The mean disease activity index and Lichtiger’s clinical activity index scores were significantly decreased after CAP(P<0.0001).The rates of steroid-free remission after the second,third,and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%,83.3%,and 60%,respectively.Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP.The rates of sustained steroid-free remission were 68.0%,60.0%,and 56.0%at 12,24,and 36 mo after the CAP.Nine patients(36%)had maintained steroid-free remission throughout the observation period.CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis

BACKGROUND Real-world data on tofacitinib(TOF)covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis(UC)are scarce.AIM To investigate the long-term efficacy and safety of TOF treatment for UC,including clinical issues.METHODS We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center.All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled.Patients were followed up until August 2020.The primary outcome was the clinical response rate at week 8.Secondary outcomes included clinical remission at week 8,cumulative persistence rate of TOF administration,colectomy-free survival,relapse after tapering of TOF and predictors of clinical response at week 8 and week 48.RESULTS The clinical response and remission rates were 66.3%and 50.5%at week 8,and 47.1%and 43.5%at week 48,respectively.The overall cumulative clinical remission rate was 61.7%at week 48 and history of anti-tumor necrosis factor-alpha(TNF-α)agents use had no influence(P=0.25).The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8(30.9%vs 88.1%;P<0.001).Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8(odds ratio:0.61,95%confidence interval:0.45-0.82,P=0.001).Relapse occurred in 45.7%of patients after TOF tapering,and 85.7%of patients responded within 4 wk after re-increase.All 6 patients with herpes zoster(HZ)developed the infection after achieving remission by TOF.CONCLUSION TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-αagents.Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF.Special attention is needed for tapering and HZ.

Emerging role of exosomes in ulcerative colitis: Targeting NOD-like receptor family pyrin domain containing 3 inflammasome

Ulcerative colitis(UC)is a chronic recurrent inflammatory bowel disease.Despite ongoing advances in our understanding of UC,its pathogenesis is yet unelu-cidated,underscoring the urgent need for novel treatment strategies for patients with UC.Exosomes are nanoscale membrane particles that mediate intercellular communication by carrying various bioactive molecules,such as proteins,RNAs,DNA,and metabolites.The NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a cytosolic tripartite protein complex whose activation induces the maturation and secretion of proinflammatory cytokines interleukin-1β(IL-1β)and IL-18,triggering the inflammatory response to a pathogenic agent or injury.Growing evidence suggests that exosomes are new modulators of the NLRP3 inflammasome,with vital roles in the pathological process of UC.Here,recent evidence is reviewed on the role of exosomes and NLRP3 inflammasome in UC.First,the dual role of exosomes on NLRP3 inflammasome and the effect of NLRP3 inflammasome on exosome secretion are summarized.Finally,an outlook on the directions of exosome-NLRP3 inflammasome crosstalk research in the context of UC is proposed and areas of further research on this topic are high-lighted.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis:A network meta-analysis

BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Are we ready to use new endoscopic scores for ulcerative colitis?

For ulcerative colitis(UC),the variability in inflammatory activity along the colon poses a challenge in management.The focus on achieving endoscopic healing in UC is evident,where the UC Endoscopic Index of Severity and Mayo Endoscopic Subscore are commonly used for evaluation.However,these indices primarily consider the most severely affected region.Liu et al recent study validates the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score offering a comprehensive assessment of inflammatory activity across diverse segments of the colon and rectum and a reliable index correlating strongly with UC Endoscopic Index of Severity and moderately with Mayo Endoscopic Subscore(MES).Despite recommendation,certain aspects warrant further invest-igation.Fecal calprotectin,an intermediate target,correlates with TIGER and should be explored.Determining TIGER scores defining endoscopic remission and response,evaluating agreement with histological activity,and assessing inter-endoscopist agreement for TIGER require scrutiny.Exploring the correlation between TIGER and intestinal ultrasound,akin to MES,adds value.

SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

Exploring the autophagy-related pathogenesis of active ulcerative colitis

BACKGROUND The pathogenesis of ulcerative colitis(UC)is complex,and recent therapeutic advances remain unable to fully alleviate the condition.AIM To inform the development of novel UC treatments,bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC.METHODS The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria.Differential analysis was conducted to obtain differentially expressed genes(DEGs).Au-tophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes(DEARGs)associated with active UC.DEARGs were then subjected to KEGG,GO,and DisGeNET disease enrichment analyses using R software.Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm.The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs,and the top five targets in the Dgree ranking were designated as core targets.RESULTS A total of 4822 DEGs were obtained,of which 58 were classified as DEARGs.SERPINA1,BAG3,HSPA5,CASP1,and CX3CL1 were identified as core targets.GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy.KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways.Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion.Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls.CONCLUSION Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Tofacitinib for ulcerative colitis: A promising treatment option

A single center retrospective clinical study revealed the efficacy and safety of tofa-citinib in the treatment of ulcerative colitis(UC).This study has clinical reference value but also has some limitations.Previous studies,including this clinical trial,have shown that tofacitinib could be a promising treatment option for UC,but further clinical research is required to prove this point.

Enhancing Ulcerative Colitis Diagnosis:A Multi-Level Classification Approach with Deep Learning

The evaluation of disease severity through endoscopy is pivotal in managing patients with ulcerative colitis,a condition with significant clinical implications.However,endoscopic assessment is susceptible to inherent variations,both within and between observers,compromising the reliability of individual evaluations.This study addresses this challenge by harnessing deep learning to develop a robust model capable of discerning discrete levels of endoscopic disease severity.To initiate this endeavor,a multi-faceted approach is embarked upon.The dataset is meticulously preprocessed,enhancing the quality and discriminative features of the images through contrast limited adaptive histogram equalization(CLAHE).A diverse array of data augmentation techniques,encompassing various geometric transformations,is leveraged to fortify the dataset’s diversity and facilitate effective feature extraction.A fundamental aspect of the approach involves the strategic incorporation of transfer learning principles,harnessing a modified ResNet-50 architecture.This augmentation,informed by domain expertise,contributed significantly to enhancing the model’s classification performance.The outcome of this research endeavor yielded a highly promising model,demonstrating an accuracy rate of 86.85%,coupled with a recall rate of 82.11%and a precision rate of 89.23%.

Game changer:How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis mana

Recent advancements in the treatment landscape of ulcerative colitis(UC)have ushered in a new era of possibilities,particularly with the introduction of Janus kinase(JAK)-signal transducer and activator of transcription inhibitors.These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes.With approved JAK inhibitors(JAKis),such as tofacitinib,filgotinib,and upadacitinib,clinicians now have powerful tools to modulate immune responses and gene expression,potentially revolutionizing the treatment algorithm for UC.Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission,presenting viable options for patients who have failed conventional therapies.Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy,particularly in patients with aggressive disease phenotypes or refractory to biologic agents.The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC,offering timely relief for patients with active disease and facilitating personalized treatment approaches.Despite safety concerns,including cardiovascular risks and infections,ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

Refractory ulcerative colitis:Upadacitinib versus other biologics

In this editorial we comment on an article published in World Journal of Clinical Cases in 2024,in which a case of refractory ulcerative colitis(UC)was discussed based on the response to different lines of biologics.Different studies showed that different classes of biologics have their advantages and disadvantages in the treatment of refractory UC.Certain classes are superior to others and if tried earlier on would lead to a possible change in the outcome.

Targeted screening of an anti-inflammatory polypeptide from Rhopilema esculentum Kishinouye cnidoblasts and elucidation of its mechanism in alleviating ulcerative colitis based on an analysis of the gut microbiota and metabolites

Ulcerative colitis(UC)is a recurrent inflammatory bowel disease that imposes a severe burden on families and society.In recent years,exploiting the potential of marine bioactive peptides for the treatment of diseases has become a topic of intense research interest.This study revealed the mechanism underlying the protective effect of the dominant polypeptide PKKVV(Pro-Lys-Lys-Val-Val)of Rhopilema esculentum cnidoblasts against DSS-induced UC through a combined analysis of the metagenome and serum metabolome.Specifically,the polypeptide composition of R.esculentum cnidoblasts was determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF/TOF-MS).Molecular docking showed that the dominant peptide PKKVV could bind better with tumor necrosis factor-α(TNF-α)than the original ligand.Subsequent animal experiments suggested that PKKVV could modulate disorganized gut microorganisms in mice with UC;affect serum metabolites through the arachidonic acid,glycerophospholipid and linoleic acid metabolism pathways;and further alleviate UC symptoms.This study provides a reference for the comprehensive development of marine bioactive substances and nonpharmaceutical treatments for UC.

Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis

Tofacitinib is an oral small-molecule Janus kinase(JAK)inhibitor that preferentially inhibits JAK1 and JAK3.Its efficacy in inducing and maintaining remission in ulcerative colitis(UC)as well as its safety profile has been demonstrated in multicenter,randomized,double-blind,placebo-controlled trials.Additionally,real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted,affirming its clinical efficacy in moderate-to-severe UC.

Structural characteristics of phenylboronic acid-modified astaxanthin ester and its effect on DSS-induced ulcerative colitis by blocking reactive oxygen species and maintaining intestinal homeostasis

A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical structure and physicochemical property were identified.AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model.Then,the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive infl ammatory models induced by LPS,copper(Cu^(2+)),high-fat diet,and dextran sodium sulfate(DSS).The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis(UC)induced by DSS.Furtherly,AstaDPBA significantly alleviated and treated weight loss and colonic shrinkage,inhibited infl ammatory cytokines,and maintained microbiota homeostasis to improve UC in C57BL/6J mice.Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test(P<0.01)of 16S rRNA gene sequencing data.In conclusion,AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.