BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithel...BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.展开更多
OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with e...OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.展开更多
Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Lite...Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.展开更多
Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is...Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed t...Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.展开更多
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of U...Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.展开更多
Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-perfo...Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.展开更多
Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t m...We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.展开更多
BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and...BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.展开更多
BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the v...BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.展开更多
Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The ai...Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine.Methods:Consecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.The median follow-up was 81 months,and all the data were analyzed in January 2021.The primary outcome was the need for step-up treatment,which included the use of corticosteroids,immunomodulatory,or surgery during admission and follow-up.Data were analyzed using the c2 or Fisher exact test,Spearman test,t-test,and ManneWhitney U test.Results:Totally,65 patients were enrolled,of whom 12(18.5%)needed step-up treatment due to nonresponse to mesalazine.The UCEIS score,MES,and the ulcerative colitis disease activity index(UCDAI)score were significantly higher in patients who had nonresponse to mesalazine(UCEIS score:6.92±0.69 vs.4.45±1.17,p<0.001;MES:2.67±0.49 vs.2.15±0.69,p=0.024;UCDAI score:9.33±1.87 vs.6.70±2.38,p=0.002).In the multivariate analysis,the UCEIS score(OR=25.65,95%CI:3.048 e45.985,p=0.003),UCDAI score(OR=1.605,95%CI:1.144e2.254,p=0.006),and C-reactive protein level(OR=1.056,95%CI:1.006e1.108,p=0.026)were independent risk factors of nonresponse.The area under the ROC curve of UCEIS was 0.95,with a sensitivity of 100%and specificity of 84.6%,a cut-off value of 6,which outperformed the MES with an area under the ROC curve of 0.70.When the UCEIS score≥6,60%of patients eventually needed step-up treatment.Conclusions:The UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine.The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score≥6.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran s...OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of li...BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.展开更多
Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,de...Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.展开更多
Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent ...Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.展开更多
Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,pri...Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.展开更多
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and debilitating inflammatory bowel disease.Cumulative evidence indicates that excess hydrogen peroxide,a potent neutrophilic chemotactic agent,produced by colonic epithelial cells has a causal role leading to infiltration of neutrophils into the colonic mucosa and subsequent development of UC.This evidence-based mechanism identifies hydrogen peroxide as a therapeutic target for reducing agents in the treatment of UC.CASE SUMMARY Presented is a 41-year-old female with a 26-year history of refractory UC.Having developed steroid dependence and never achieving complete remission on treatment by conventional and advanced therapies,she began treatment with oral R-dihydrolipoic acid(RDLA),a lipid-soluble reducing agent with intracellular site of action.Within a week,rectal bleeding ceased.She was asymptomatic for three years until a highly stressful experience,when she noticed blood in her stool.RDLA was discontinued,and she began treatment with oral sodium thiosulfate pentahydrate(STS),a reducing agent with extracellular site of action.After a week,rectal bleeding ceased,and she resumed oral RDLA and discontinued STS.To date,she remains asymptomatic with normal stool calprotectin while on RDLA.CONCLUSION STS and RDLA are reducing agents that serve as highly effective and safe therapy for the induction and maintenance of remission in UC,even in patients refractory or poorly controlled by conventional and advanced therapies.Should preliminary findings be validated by subsequent clinical trials,the use of reducing agents could potentially prevent thousands of colectomies and represent a paradigm shift in the treatment of UC.
基金Supported by Shandong Provincial Natural Science,Study on the Structure-Activity Relationship and Mechanism of Licorice Chalcone Components in Synergizing with Immune Checkpoint Inhibitors for Anticancer Therapy(No.ZR2020MH380)Mechanisms of the Novel Flavone C-Glycoside 6'-ORhamnosyllutonarin from Dianthus superbus Improves Non-alcoholic Fatty Liver Disease via Modulating the Juxtaposed with Another Zinc Finger gene 1/Adenosine Monophosphate-activated Protein Kinase/Sterol Regulatory Element-Binding Protein Pathway(No.ZR2024MC209)。
文摘OBJECTIVE:To explore the mechanism of Baitouweng Tang(白头翁汤,Pulsatilla decoction,PD)alleviates dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice by integrating network pharmacology prediction with experimental validation,focusing on the modulation of inflammatory signaling.METHODS:A chronic UC model was induced in C57BL/6 mice by cyclical administration of DSS.Mice were treated with either a low(15 m L/kg)or high(30 m L/kg)dose of PD.Disease severity was assessed clinically and via histopathology.Serum levels of inflammatory cytokines were quantified.A network pharmacology approach was employed to predict the core targets and pathways of PD against UC.Key predictions concerning the toll-like receptor 4/nuclear factor-kappa B(TLR4/NF-κB)pathway were subsequently verified in colonic tissue using quantitative polymerase chain reaction and Western blotting.RESULTS:PD treatment significantly ameliorated DSSinduced UC symptoms,including reducing disease activity,preventing colon shortening,and improving histological architecture.PD effectively rebalanced the systemic inflammatory milieu by decreasing proinflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)and elevating anti-inflammatory cytokines interleukin-10(IL-10).Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a central target.Experimental validation confirmed that PD markedly suppressed the upregulation of both TLR4 and NF-κB at the transcriptional and protein levels in the inflamed colon.CONCLUSION:PD demonstrates protective effects against experimental UC.Its mechanism is associated with the inhibition of the TLR4/NF-κB signaling pathway and the subsequent attenuation of inflammatory responses.This study provides a modern pharmacological basis for the classical application of PD in treating heat-toxin related intestinal disorders,bridging traditional use and mechanistic understanding.
基金financial support from the Postdoctoral Fund of Hebei Medical University(30705010038)the Chunyu Project Initial Funding of Hebei Medical University(CYQD2023012)+3 种基金the Science Research Project of Hebei Education Department(QN2025145)the Hebei Yanzhao Golden Platform Talent Gathering Plan Backbone Talent Project(B2024003013)the Natural Science Foundation of Hebei Province(H2024206375,C2022206018,H2023206068)the Traditional Chinese Medicine Administration Project of Hebei Province(2025427).
文摘Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.
基金financially supported by the Science and Technology Project of Nantong City(Grant No.JC2021097)the Key Project Fund for Clinical Medicine Special Program of Nantong University(Grant No.2024JZ043)Jiangsu Provincial Administration for Market Regulation Science and Technology Program Project(Grant No.KJ2026104).
文摘Background:Jianpi Huazhi Wan(JPHZW)is the hospital preparation of Nantong Hospital of Traditional Chinese Medicine.The clinical effect of JPHZW on gastrointestinal diseases is remarkable,but its mechanism of action is not clear.This study aimed to investigate the therapeutic effects of JPHZW and explore its mechanism of action through colonic transcriptomics and gut microbiota analysis.Methods:An ulcerative colitis(UC)mice model was established to evaluate the therapeutic effect of JPHZW.The expression levels of specific inflammatory factors in colon tissue were determined by ELISA.Colonic transcriptome sequencing was performed to identify candidate targets.The effects of JPHZW on gut microbiota were analyzed using 16S rRNA sequencing.Finally,relevant signaling pathways were verified via Western blotting to elucidate the mechanism of action of JPHZW.Results:JPHZW significantly improved the DAI Score and reduced the expression levels of pro-inflammatory factors,such as MCP-1,IL-17A,and IFN-γ,while increasing the expression levels of anti-inflammatory factors,such as IL-4,EGF,and GM-CSF in UC mice.Colonic transcriptome sequencing revealed that the Peroxisome PPAR-γ/NF-κB signaling pathway was closely associated with JPHZW’s anti-UC effect.Furthermore,WB analysis demonstrated that JPHZW treatment significantly inhibited the upregulation the expression of NF-κB and significantly upregulated the expression of PPAR-γ.In addition,16S rRNA sequencing analysis indicated that the relative abundance of beneficial bacteria was improved.Conclusion:These findings demonstrate that JPHZW alleviates DSS-induced ulcerative colitis in mice by regulating the PPAR-γ/NF-κB signaling pathway to suppress inflammatory factors,while simultaneously improving gut microbiota composition by increasing the relative abundance of beneficial bacteria.
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金financially supported by the Major Science and Technology Special Projects in Henan Province(231100310200)the Key R&D Projects in Henan Province(241111314200)+1 种基金the National Natural Science Foundation of China(32302172)the Natural Science Foundation of Henan Province(252300423038).
文摘Ulcerative colitis(UC)is a chronic intestinal inflammatory disease characterized by a complex pathogenesis.Weizmannia coagulans has emerged as a potential probiotic for treating intestinal disorders.This study aimed to assess the therapeutic impact of W.coagulans BC99 on mice with DSS-induced UC and to elucidate its underlying mechanism of action.Our findings revealed that BC99 administration ameliorated symptoms associated with DSS-induced UC mice,as evidenced by reduced disease activity indexes,reversal of weight loss,and normalization of colon length.Furthermore,BC99 treatment also protected the integrity of the intestinal barrier through maintaining the antioxidant activity and the expression of tight junction proteins(ZO-1 and occludin),and regulating the inflammatory cytokines in DSS-induced UC mice.Additionally,BC99 supplementation enhanced the production of short-chain fatty acids(SCFAs)through the proliferation of SCFA-producing bacteria,including Bidobacterium,Blautia and Faecallbaculum.Notably,the NF-κB signaling pathway was found to be closely related to BC99 treatment in DSS-induced UC mice.The positive protein expression and the m RNA expression of TLR4,My D88 and p65 in colon tissue were all detected in BC99-treated groups,which indicating that BC99 could alleviate UC symptoms by inhibiting TLR4/My D88/NF-κB signaling pathway.Metabolomics further confirms the previous results.Collectively,these findings provide basic support for the W.coagulans as a functional food additive or a promising therapeutic agent for the effective management of UC.
基金Supported by National Natural Science Foundation of China,No.82374200Construction of Traditional Chinese Medicine Inheritance and Innovation Development Demonstration Pilot Projects in Pudong New Area-High-Level Research-Oriented Traditional Chinese Medicine Hospital Construction,No.YC-2023-0901.
文摘Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized byclinical symptoms of diarrhea and mucopurulent bloody stools, and its incidenceis increasing globally. The etiology and pathogenesis of UC remain elusive. Currenttherapeutic approaches, including anti-inflammatory, immunosuppressiveand immunomodulating agents, are often limited in efficacy and frequently associatedwith adverse drug reactions. Therefore, there is an urgent need to developsafer and more effective treatment strategies to address the limitations of existingtherapies. Scutellaria baicalensis Georgi (HQ), a traditional Chinese medicinal herb,has been employed in the treatment of UC for over 2000 years. Recent studieshave demonstrated that HQ contains multiple active components capable oftreating UC through anti-inflammation, immune modulation, intestinal barrierprotection, antioxidant activity, and regulation of the gut microbiota. This paperreviews recent studies on the mechanism of action and clinical trials of HQ intreating UC based on relevant literature, with the aim of providing valuable insightsinto future treatment approaches.
基金supported by the Key Research and Development Project of Hainan Province(ZDYF2022SHFZ099)the Academic Enhancement Support Program of Hainan Medical University(XSTS2025040 and XSTS2025063).
文摘Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
文摘We read with great interest the study by Zhang et al on Yiyi Fuzi Baijiang powder(YFB),which exemplifies the power of modern methods to validate traditional Chinese medicine(TCM).The key insight is that YFB doesn’t merely alter“good”or“bad”bacteria but restores the gut microbiota’s holistic equilibrium.This is powerfully shown by its paradoxical reduction of anaerobic probiotics like Bifidobacterium,rectifying the diseased,hypoxic environment,causing their aberrant overgrowth.This challenges the conventional probiotic paradigm and underscores a core TCM principle:Herbal formulas treat disease by restoring the body’s overall functional balance.Future research should focus on the interplay between herbal components,intestinal oxygen,and microbial metabolites to further unravel this sophisticated dialogue.
文摘BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.
基金Supported by Wenzhou Science and Technology Bureau,No.Y2020296.
文摘BACKGROUND Ulcerative colitis(UC)is usually diagnosed through histopathology,enteroscopy,clinical symptoms,and physical findings;however,it is difficult to accurately evaluate disease severity.AIM To investigate the value of endoscopic ultrasonography(EUS)in the evaluation of the severity and prognosis of UC.METHODS Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible,and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores.We performed EUS,calculated the UC endoscopic index of severity(UCEIS)and EUS-UC scores,and administered appropriate treatment.The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity,and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed.The UCEIS and EUS-UC scores before and after treatment were also compared.RESULTS A total of 79 patients were included in this study.According to the Mayo Index,23,32,and 24 patients had mild,moderate and severe UC,respectively.The UCEIS and EUS-UC scores were higher in moderate cases(4.98±1.04 and 5.01±0.99,respectively)than in mild cases(1.56±0.82 and 1.64±0.91,respectively,P<0.05).Furthermore,the UCEIS and EUS-UC scores(7.31±1.10 and 7.59±1.02,respectively)were higher in severe cases than in moderate cases(P<0.05).According to the modified Truelove and Witts scores,21,36,and 22 patients were classified as having mild,moderate and severe disease,respectively.The UCEIS and EUS-UC scores were significantly higher in moderate disease(4.79±1.11 and 4.96±1.23,respectively)than in mild disease(1.71±0.78 and 1.69±0.88,respectively,P<0.05).Additionally,the UCEIS and EUS-UC scores in severe disease(7.68±1.22 and 7.81±0.90,respectively)were significantly higher than in moderate disease(P<0.05).The UCEIS and EUSUC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score(P<0.05).The UCEIS and EUS-UC scores after 2 mo of treatment(3.88±0.95 and 4.01±1.14,respectively)and after 6 mo of treatment(1.59±0.63 and 1.64±0.59,respectively)were lower than the respective scores before treatment(5.93±1.79 and 6.04±2.01)(P<0.05).CONCLUSION EUS can clarify the status of UC and accurately evaluate the treatment response,providing an objective basis for formulation and adjustment of the treatment plan.
基金the Natural Science Foundation of Zhejiang Province(LQ21H030010&Q19H030064)Medical Health Science and Technology Project of the Zhejiang Provincial Health Commission(2021417815).
文摘Objective:The ulcerative colitis endoscopic index of severity(UCEIS)and the Mayo endoscopic score(MES)are developed as objective methods of evaluating endoscopic severity in patients with ulcerative colitis(UC).The aim of this study is to investigate the diagnostic accuracy of the UCEIS and MES in predicting the patient's response to mesalazine.Methods:Consecutive patients with UC who had undergone colonoscopy within 1 month before starting mesalazine between October 2011 and July 2016 were retrospectively collected at the Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine.The median follow-up was 81 months,and all the data were analyzed in January 2021.The primary outcome was the need for step-up treatment,which included the use of corticosteroids,immunomodulatory,or surgery during admission and follow-up.Data were analyzed using the c2 or Fisher exact test,Spearman test,t-test,and ManneWhitney U test.Results:Totally,65 patients were enrolled,of whom 12(18.5%)needed step-up treatment due to nonresponse to mesalazine.The UCEIS score,MES,and the ulcerative colitis disease activity index(UCDAI)score were significantly higher in patients who had nonresponse to mesalazine(UCEIS score:6.92±0.69 vs.4.45±1.17,p<0.001;MES:2.67±0.49 vs.2.15±0.69,p=0.024;UCDAI score:9.33±1.87 vs.6.70±2.38,p=0.002).In the multivariate analysis,the UCEIS score(OR=25.65,95%CI:3.048 e45.985,p=0.003),UCDAI score(OR=1.605,95%CI:1.144e2.254,p=0.006),and C-reactive protein level(OR=1.056,95%CI:1.006e1.108,p=0.026)were independent risk factors of nonresponse.The area under the ROC curve of UCEIS was 0.95,with a sensitivity of 100%and specificity of 84.6%,a cut-off value of 6,which outperformed the MES with an area under the ROC curve of 0.70.When the UCEIS score≥6,60%of patients eventually needed step-up treatment.Conclusions:The UCEIS is a useful instrument for predicting the therapeutic effect in patients with UC treated with mesalazine.The high probability of mesalazine treatment failure and benefits of other therapies should be discussed in patients with baseline UCEIS score≥6.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
基金National Natural Science Foundation of China:Study for the Mechanism of Moxibustion in Ulcerative Colitis based on the α7 Nicotinic Acetylcholine Receptor Mediated Cholinergic Antiinflammatory Pathway (No.82205293)National Natural Science Foundation of China:Study of the Central Nervous System Regulatory Mechanism of Moxibustion Repair of Ulcerative Colitis Gut Vascular Barrier Based on Ubiquitin Specific Peptidase 14 Deubiquitination (No.82274641)+3 种基金National Natural Science Foundation of China:Moxibustion Regulates P300-mediated Histone H3K27 Acetylation Modification in the Treatment of Crohn's Disease (No.82205262)National Natural Science Foundation of China:Study on the Protective Mechanism of Moxibustion on Intestinal Mucosal Barrier in Ulcerative Colitis based on GABAergic System (No.82105012)Shanghai Sailing Program:to Study the Protective Effect of Moxibustion on Intestinal Mucosal Barrier in Crohn's Disease Based on Histone H3 Acetylation Modification (No.22YF1444100)State Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project (No.zyyzdxk-2023068)。
文摘OBJECTIVE:To investigate the effect and mechanism of mild moxibustion on the non-neuronal cholinergic system(NNCS) in rats with ulcerative colitis(UC).METHODS:UC rat model was established by administering 4% dextran sulfate sodium.After 7 d,mild moxibustion,α7 nicotinic acetylcholine receptors(α7nAchRs) antagonist(α-bungarotoxin,α-BGT),vesicular acetylcholine transport inhibitor(vesamicol hydrochloride,VH) and organic cation transporters inhibitor(quinine,Qu) treatments were performed once daily for 7 d.Haematoxylin and eosin staining was used for morphological evaluation of colon tissues.Enzymelinked immunosorbent assay(ELISA) was used to measure the protein expressions of interleukin-1β(IL-1β) and choline acetyltransferase(ChAT) in colon tissue.Reverse transcription quantitative real-time polymerase chain reaction(RT-q PCR) was used to detect the mRNA expressions of IL-1β,carnosine acetyltransferase(CarAT),ChAT,and nuclear factor kappa-B p65 subunit(NF-κB p65) in colon tissue.Western blot was used to detect NF-κB p65 protein expression in colon tissue.Immunofluorescence was used to detect the expressions of neuronal acetylcholine(nAch) and non-neuronal acetylcholine(nnAch,released by NNCS) in colon tissue.RESULTS:Mild moxibustion inhibited colon inflammation and repaired mucosal damage to the colon in UC rats.Meanwhile,mild moxibustion could downregulate the expressions of IL-1β,NF-κB p65 protein and mRNA(P < 0.01),and upregulate the expressions of ChAT protein and CarAT mRNA(P < 0.05,P < 0.01).The α7nAChR antagonist α-BGT can reverse the protective effect of mild moxibustion on the UC and the inhibitory effect on the inflammatory factors.VH cannot affect the effect of mild moxibustion on the expressions of IL-1β and nnAch,while Qu can reverse the effect of mild moxibustion on the expression of IL-1β and nnAch.CONCLUSIONS:Mild moxibustion can inhibite colon inflammation in UC rats,which is closely related to the release of acetylcholine by NNCS and its mediated mechanism of cholinergic anti-inflammation pathway.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon.The most common psychological issue in UC patients is varying degrees of depre-ssion,which affects the condition and quality of life of UC patients and may lead to deterioration of the patient’s condition.UC drugs combined with anti-anxiety and antidepression drugs can alleviate symptoms of both depression and UC.Brain-derived neurotrophic factor(BDNF)precursor(proBDNF)/p75 neurotrophin receptor(p75NTR)/sortilin and BDNF/tropomyosin receptor kinase B(TrkB)signalling balance is essential for maintaining brain homeostasis and preventing the development of depressive behaviours.AIM To explore the mechanism by which Wuling powder regulates the proBDNF/p75NTR/sortilin and BDNF/TrkB pathways in the treatment of UC with depre-ssion.METHODS Depression was established in C57BL/6J mice via chronic restraint stress,and the UC model was induced with dextran sodium sulfate(DSS).In the treatment stage,mesalazine(MS)was the basic treatment,Wuling powder was the experimental treatment,and fluoxetine was the positive control drug for treating depression.Changes in intestinal mucosal inflammation,behaviour,and the proBDNFp75NTR/sortilin and BDNF/TrkB pathways were evaluated.RESULTS In the depression groups,Wuling powder decreased the immobility time,increased the distance travelled in the central zone and the total distance travelled,and restored balance in the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways.In the DSS and chronic restraint stress+DSS groups,immobility time increased,distance travelled in the central zone and total distance travelled decreased,activity of the proBDNF/p75NTR/sortilin pathway was upregulated,and activity of the BDNF/TrkB pathway was downregulated,indicating that mice with UC often have comorbid depression.Compared with those of MS alone,Wuling powder combined with MS further decreased the colon histopathological scores and the expression levels of tumor necrosis factor-alpha and interleukin-6 mRNAs.CONCLUSION This study confirmed that Wuling powder may play an antidepressant role by regulating the balance of the proBDNF/p75NTR/sortilin and BDNF/TrkB signalling pathways and further relieve intestinal inflammation in UC.
文摘Ulcerative colitis has baffled researchers since the early 20th century.The pre-vailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality,despite the lack of supporting evidence.This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease.By analyzing existing data from less than a dozen previously published studies,a novel,evidence-based pathogenesis was constructed,implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease.This newly identified mechanism informed the creation of a ground-breaking class of therapeutics,known as reducing agents,which have demon-strated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis.This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.
文摘Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis.Management of myocarditis is primarily supportive,because there are currently no established targeted therapies.Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis.Here,we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis.The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation,suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.
基金Supported by Tianjin Municipal Science and Technology Commission Grant,No.24ZXRKSY00010Program for Innovative Research Team in Peking Union Medical College,CAMS Initiative for Innovative Medicine,No.2023-I2M-2-008.
文摘Inflammatory bowel disease(IBD)is an incurable disease of the digestive system;however,the therapeutic methods for IBD remain limited.The pathogenesis of IBD was systematically discussed and compared in this paper,primarily comprising Crohn’s disease and ulcerative colitis.This paper focused on six common aspects:(1)Dysregulated immune responses;(2)Gene function changes;(3)Intestinal microbes disorder and imbalance;(4)Microbial infections;(5)Associations between IBD and other inflammatory diseases;and(6)Other factors.In addition,the pathogenesis differences between these two forms of IBD were unraveled and clearly distinguished.These unique aspects of pathogenesis provide crucial insights for the precise treatment of both Crohn’s disease and ulcerative colitis.This paper illustrates the root causes and beneficial factors of resistance to IBD,which provides novel insights on early prevention,development of new therapeutic agents,and treatment options of this disease.
