Treatment Of Ulcerative Colitis Research Articles

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study.

The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.

Trends in Public Drug Plan Expenditures for Patients With Crohn Disease and Ulcerative Colitis Initiating Targeted Immune Modulator Therapy

The objective of this analysis was to examine the changes in drug expenditures with the initiation of targeted immune modulator (TIM) treatment in patients diagnosed with Crohn disease (CD) and ulcerative colitis (UC). Patient cohorts for CD and UC were identified from hospitalizations in Canada. Expenditure data for TIMs with a Health Canada–approved indication for the treatment of CD or UC were extracted from all provincial drug plans (except Quebec) and Yukon from 2016 to 2021, and a descriptive analysis was performed to assess the expenditure patterns. Annual expenditures on TIMs for patients with CD increased each year from 2016 to 2019 before decreasing in 2020 and 2021, whereas expenditures on TIMs in UC increased each year, generally by a greater percentage than was observed in CD (peak percentage growth of 92.5% for UC versus 15.9% for CD in 2018). Expenditures associated with TIM initiation among patients with CD and UC were driven by infliximab and adalimumab, with the 2 drugs accounting for nearly all expenditures in both indications in 2016 and most expenditures in 2021. In both CD and UC, vedolizumab expenditures increased over time, as did the proportions of TIM expenditures on ustekinumab in CD and tofacitinib in UC, albeit to a lesser extent than vedolizumab.

Modified Zhenwu Decoction improved intestinal barrier function of experimental colitis through activation of sGC-mediated cGMP/PKG signaling

BackgroundThe invasion of luminal antigens and an aberrant immune response resulting from a disrupted physical epithelial barrier are the key characteristics of ulcerative colitis (UC). The restoration of damaged epithelial function is crucial for maintaining mucosal homeostasis and disease quiescence. Current therapies for UC primarily focus on suppressing inflammation. However, most patients fail to respond to therapy or develop secondary resistance over time, emphasizing the need to develop novel therapeutic targets for UC. Our study aimed to identify the potential targets of a novel modified herbal formula from the Zhen Wu Decoction, namely CDD-2103, which has demonstrated promising efficacy in treating chronic colitis. MethodsThe effect of CDD-2103 on epithelial barrier function was examined using in vitro and ex vivo models of tissue injury, as well as a chronic colitis C57BL/6 mouse model. Transcriptomic analysis was employed to profile gene expression changes in colonic tissues following treatment with CDD-2103. ResultsOur in vivo experiments demonstrated that CDD-2103 dose-dependently reduced disease severity in mice with chronic colitis. The efficacy of CDD-2103 was mediated by a reduction in goblet cell loss and the enhancement of tight junction protein integrity. Mechanistically, CDD-2103 suppressed epithelial cell apoptosis and tight junction protein breakdown by activating the soluble guanynyl cyclase (sGC)-mediated cyclic guanosine monophosphate (cGMP)/PKG signaling cascade. Molecular docking analysis revealed strong sGC ligand recognition by the CDD-2103-derived molecules, warranting further investigation. ConclusionOur study revealed a novel formulation CDD-2103 that restores intestinal barrier function through the activation of sGC-regulated cGMP/PKG signaling. Furthermore, our findings suggest that targeting sGC can be an effective approach for promoting mucosal healing in the management of UC.

Self-assembled nanoparticles of costunolide and glycyrrhizic acid for enhanced ulcerative colitis treatment

Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π–π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition.

Protective effects of ginsenosides on ulcerative colitis: a meta-analysis and systematic review to reveal the mechanisms of action.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Ginsenoside may be an ideal agent for UC treatment. However, its efficacy and safety are unknown. We aim to conduct a systematic evaluation to assess the effects and potential mechanisms of ginsenosides in animal models of UC. Six electronic databases will be searched (PubMed, Embase, Web of Science, China Knowledge Network (CNKI), China Science and Technology Journal Database (CQVIP), and Wanfang Data Knowledge). SYRCLE list will be used to assess the quality of literature, and STATA 15.1 for data analysis. Time-dose effects analysis will be used to reveal the time-dosage response relations between ginsenosides and UC. Ultimately, fifteen studies involving 300 animals were included. Preliminary evidence was shown that ginsenosides could reduce Disease Activity Index (DAI) scores, weight loss, histological colitis score (HCS), spleen weight, Malondialdehyde (MDA), Myeloperoxidase (MPO) activity, interleukin-1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and increase colon length (CL), myeloperoxidase (GSH), interleukin 4 (IL-4), interleukin 10 (IL-10), Zonula Occludens-1 (ZO-1) and occludin. Results of time-dose interval analysis indicated that ginsenosides at a dosage of 5-200mg/kg with an intervention time of 7-28days were relatively effective. Preclinical evidence suggests that ginsenoside is a novel treatment for UC. And the mechanisms of ginsenosides in treating UC may involve anti-inflammatory, antioxidant, barrier protection, intestinal flora regulation, and immune regulation. Although, due to the high heterogeneity, further large-scale and high-quality preclinical studies are needed to examine the protection of ginsenosides against UC.

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

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

Neohesperidin Dihydrochalcone Ameliorates Experimental Colitis via Anti-Inflammatory, Antioxidative, and Antiapoptosis Effects.

Neohesperidin dihydrochalcone (NHDC) is a citrus-originated, seminatural sweetener. There is no investigation concerning the effect of NHDC on ulcerative colitis. The purpose of this study was to determine the therapeutic and protective effects of NHDC in Wistar Albino rats. NHDC was given for 7 days after or before colitis induction. The results showed that NHDC significantly reduced the interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels. Catalase levels did not show a significant difference between the groups. NHDC provided a remarkable decrease in the expression levels of cyclooxygenase-2 (COX-2), myeloperoxidase (MPO), malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB). Total antioxidant status (TAS) levels were significantly elevated in NHDC treatment groups, while total oxidant status (TOS) and oxidative stress index (OSI) levels were significantly decreased. NHDC provided remarkable improvement in histological symptoms such as epithelial erosion, edema, mucosal necrosis, inflammatory cell infiltration, and hemorrhage. Also, caspase-3 expression levels were statistically decreased in NHDC treatment groups. The results indicated that NHDC might be a protection or alternative treatment for ulcerative colitis.

The First Discovery of Marine Polyoxygenated Cembranolides as Potential Agents for the Treatment of Ulcerative Colitis.

Cembranolides are characteristic metabolites in marine soft corals, with complex structures and widespread biological activities. However, seldom has an intensive pharmacological study been done for these intriguing marine natural products. In this work, systematic chemical investigation was performed on Sinularia pedunculata by HSQC-based small molecule accurate recognition technology (SMART), resulting in the isolation and identification of 31 cembrane-type diterpenoids, including six new ones. In the bioassay, several compounds showed significant anti-inflammatory activities on the inhibition of NO production. The structure-activity relationship (SAR) was comprehensively analyzed, and two most bioactive and less toxic compounds 8 and 9 could inhibit inflammation through suppressing NF-κB and MAPK signaling pathways, and reduce the secretion of inflammatory cytokines. In a mouse model of dextran sodium sulfate (DSS)-induced acute colitis, 8 and 9 exhibited good anti-inflammatory effects and the ability to repair the colon epithelium, giving insight into the application of cembranolides as potential ulcerative colitis (UC) agents.

2023 Chinese national clinical practice guideline on diagnosis and management of ulcerative colitis.

2023 Chinese national clinical practice guideline on diagnosis and management of ulcerative colitis.

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 mRNA 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.

Systematically investigate the mechanism underlying the therapeutic effect of Astragalus membranaceus in ulcerative colitis

BackgroundWhether Astragalus membranaceus is an effective drug in treatment of ulcerative colitis (UC) and how it exhibit activity effect on UC is unclear. MethodsTCMSP, GeneCards, String, and DAVID database were used to screening target genes construct PPI network and performed for GO and KEGG pathway enrichment analysis respectively. Molecular docking and animal experiment were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measured the expressions of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins. ResultsThe active components of Astragalus membranaceus mainly including 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibited the expression of TNF-α, IL-6, MDA, and promoted the expression of CAT, SOD, IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased administrated with Astragalus membranaceus. ConclusionsAstragalus membranaceus is an effective drug in treatment of UC according to related to above targets that may exhibits the anti-UC effect via its antioxidant pathway and regulating the balance of pro-inflammatory and anti-inflammatory factors.

Paeoniae Decoction restores intestinal barrier dysfunction by promoting the interaction between ILC3 and gut flora

BackgroundIntestinal barrier dysfunction is a significant contributor to the recurrence and refractory of ulcerative colitis (UC). Promoting the interaction between group 3 innate lymphoid cells (ILC3s) and gut flora is a valuable strategy for mucosal repair. Paeoniae decoction (PD) is a compound commonly used in clinical treatment of UC, but its exact mechanism remains unclear. PurposeWe aimed to investigate the protective effect of PD on intestinal mucosal injury induced by dextran sulfate sodium (DSS) in chronic colitis, as well as to elucidate its potential mechanism. MethodsC57BL/6 mice were induced with chronic colitis by 2% DSS and divided into four groups: control group, model group, PD low dose (4 g/kg), and high dose (8 g/kg) group. The effectiveness of PD in treating chronic colitis mice was evaluated based on changes in body weight, colon length, colon pathological tissue scores, and the mRNA levels of inflammatory factors IL-6 and IL-1β. The expressions of intestinal epithelial tight junction proteins (ZO-1 and Occludin), IL-22, and MUC2 were observed using immunofluorescence and RT-PCR. Additionally, the proportion of ILC3 and natural cytotoxicity receptor (NCR)+ ILC3 in the colon were detected using flow cytometry. Furthermore, UHPLC-QE-MS was utilized to identify chemical components of PD and network pharmacology was employed to predict potential pathways for PD intervention in UC. Subsequently, MNK-3 cells (ILC3 in vitro cell line) and NCM460 cells were used to verify the network pharmacology results. Finally, the effects of PD on UC gut flora have been explored using in vitro fermentation and 16S rDNA techniques. ResultsThe results showed that PD significantly restored body weight and colon length in mice with chronic colitis, while also reducing colon inflammatory cell infiltration and the expression of IL-6 and IL-1β. Additionally, PD notably promoted the expression of MUC2, ZO-1, Occludin, and IL-22, as well as increasing the ratio of ILC3 and NCR+ILC3. UHPLC-QE-MS analysis identified 443 components of PD, and network pharmacology suggested that PD could target the aryl hydrocarbon receptor (AHR) signaling pathway. which was confirmed by MNK-3 cells and in vitro fermentation experiments. Furthermore, MNK-3-conditioned medium (CM) increased the expression of ZO-1 and Occludin in NCM460 cells. In addition, 16S rDNA results indicated that PD promoted the abundance of Lactobacillales, thus contributing to mucosal damage repair by activating the AHR signal in ILC3s. ConclusionIn summary, our study demonstrates that PD repairs intestinal mucosal damage in chronic colitis by regulating the interaction of gut flora with ILC3, and the specific mechanism is related to the activation of AHR signaling pathway.

Combined gut microbiome and metabolomics to reveal the mechanism of proanthocyanidins from the roots of Ephedra sinica Stapf on the treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that primarily affects mucosa and submucosa of colon and rectum. Although the exact etiology of UC remains elusive, increasing evidence has demonstrated that the gut microbiome and its interaction with host metabolism plays an important role in UC development. The objective of this study was to investigate the therapeutic potential and mechanism of dimeric proanthocyanidins (PAC) enriched from ethyl acetate extract of Ephedra roots on UC from the perspective of gut microbiota and metabolic regulation. In this study, a bio-guided strategy integrating LC-MS analysis, DMAC assay, antioxidant screening, and antiinflammation activity screening was used to enrich dimeric PAC from Ephedra roots, then untargeted metabolomics combined with gut microbiota analysis was performed to investigate the therapeutic mechanism of PRE on UC. This is the first study that combines a bio-guided strategy to enrich dimeric PAC from Ephedra roots and a comprehensive analysis of their effects on gut microbiota and host metabolism. Oral administration of PRE was found to significantly relieve dextran sodium sulfate (DSS)-induced ulcerative colitis symptoms in mice, characterized by the reduced disease activity index (DAI), increased colon length and improved colon pathological damage, together with the down-regulation of colonic inflammatory and oxidative stress levels. In addition, 16S rRNA sequencing combined with untargeted metabolomics was conducted to reveal the effects of PRE on gut microbiota composition and serum metabolites. PRE improved gut microbiota dysbiosis through increasing the relative abundance of beneficial bacteria Lachnospiraceae_NK4A136_group and decreasing the level of potentially pathogenic bacteria such as Escherichia-Shigella. Serum metabolomics showed that the disturbed tryptophan and glycerophospholipid metabolism in UC mice was restored after PRE treatment. Collectively, PRE was proved to be a promising anti-UC candidate, which deserves further investigation in future research.

Integrating 16 S rRNA gene sequencing and metabolomics analysis to reveal the mechanism of Angelica sinensis oil in alleviating ulcerative colitis in mice

Angelica sinensis (Oliv.) Diels (AS) is a commonly used herbal medicine and culinary spice known for its gastrointestinal protective properties. Angelica sinensis oil (AO) is the main bioactive component of AS. However, the therapeutic effects and mechanisms of AO on the gastrointestinal tract remain unclear. In this study, we aim to investigated the potential of AO in restoring gut microbiota disorder and metabolic disruptions associated with ulcerative colitis (UC). A systematic chemical characterization of AO was conducted using GC×GC-Q TOF-MS. A UC mouse model was established by freely drinking DSS to assess the efficacy of AO. Utilizing 16S rRNA sequencing in combination with untargeted metabolomics analysis of serum, we identified alterations in gut microbiota, differential metabolites, and pathways influenced by AO in UC treatment, thereby elucidating the therapeutic mechanism of AO in UC management. Pharmacodynamic results indicated that AO effectively inhibited the content of inflammation mediators, such as Interleukin-1β, Interleukin-6 and tumor necrosis factor-α, and proserved colon tissue integrity in UC mice. Furthermore, AO significantly downregulated the abundance of pathogenic bacteria (Bacteroidetes, Proteobacteria, and Desulfobacteriaceae) while increasing the abundance of beneficial bacteria (Firmicutes, Blautia, Akkermansia, and Lachnospiraceae). Metabolomics analysis highlighted significant disruptions in endogenous metabolism in UC mice, with a notable restoration of SphK1 and S1P levels following AO administration. Besides, we discovered that AO regulated the balance of sphingolipid metabolism and protected the intestinal barrier, potentially through the SphK1/MAPK signaling pathway. Overall, this study indicated that AO effectively ameliorates the clinical manifestations of UC by synergistically regulating gut microbe and metabolite homeostasis. AO emerges as a potential functional and therapeutic ingredient for UC treatment.

Deciphering the shared mechanisms of Gegen Qinlian Decoction in treating type 2 diabetes and ulcerative colitis via bioinformatics and machine learning.

Although previous clinical studies and animal experiments have demonstrated the efficacy of Gegen Qinlian Decoction (GQD) in treating Type 2 Diabetes Mellitus (T2DM) and Ulcerative Colitis (UC), the underlying mechanisms of its therapeutic effects remain elusive. This study aims to investigate the shared pathogenic mechanisms between T2DM and UC and elucidate the mechanisms through which GQD modulates these diseases using bioinformatics approaches. Data for this study were sourced from the Gene Expression Omnibus (GEO) database. Targets of GQD were identified using PharmMapper and SwissTargetPrediction, while targets associated with T2DM and UC were compiled from the DrugBank, GeneCards, Therapeutic Target Database (TTD), DisGeNET databases, and differentially expressed genes (DEGs). Our analysis encompassed six approaches: weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, single-cell sequencing analysis, machine learning, DEG analysis, and network pharmacology. Through GO and KEGG analysis of weighted gene co-expression network analysis (WGCNA) modular genes and DEGs intersection, we found that the co-morbidity between T2DM and UC is primarily associated with immune-inflammatory pathways, including IL-17, TNF, chemokine, and toll-like receptor signaling pathways. Immune infiltration analysis supported these findings. Three distinct machine learning studies identified IGFBP3 as a biomarker for GQD in treating T2DM, while BACE2, EPHB4, and EPHA2 emerged as biomarkers for GQD in UC treatment. Network pharmacology revealed that GQD treatment for T2DM and UC mainly targets immune-inflammatory pathways like Toll-like receptor, IL-17, TNF, MAPK, and PI3K-Akt signaling pathways. This study provides insights into the shared pathogenesis of T2DM and UC and clarifies the regulatory mechanisms of GQD on these conditions. It also proposes novel targets and therapeutic strategies for individuals suffering from T2DM and UC.

Unraveling the mechanism of malancao in treating ulcerative colitis: A multi-omics approach

BACKGROUND Malancao (MLC) is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis (UC). Nevertheless, the precise molecular mechanisms underlying its efficacy remain elusive. This study leveraged ultra-high-performance liquid chromatography coupled with exactive mass spectrometry (UHPLC-QE-MS), network pharmacology, molecular docking (MD), and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management. AIM To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing. METHODS This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples. Furthermore, the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets. Additionally, the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC. Finally, MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential. RESULTS Firstly, through a comprehensive analysis of UHPLC-QE-MS data and public database resources, we identified 146 drug-disease cross targets related to 11 bioactive components. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management, lipid metabolism, atherosclerosis, and other processes. They also affect AGE-RAGE and apoptosis signaling pathways. Secondly, by analyzing the differences in diseases, we identified key research targets. These core targets are related to 11 active substances, including active ingredients such as quercetin and luteolin. Finally, MD analysis revealed the stability of compound-protein binding, particularly between JUN-Luteolin, JUN-Quercetin, HSP90AA1-Wogonin, and HSP90AA1-Rhein. Therefore, this suggests that MLC may help alleviate intestinal inflammation in UC, restore abnormal lipid accumulation, and regulate the expression levels of core proteins in the intestine. CONCLUSION The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway. The amalgamation of botanical resources, metabolomics, natural products, MD, and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

Cu,Zn,I-Doped Carbon Dots with Boosted Triple Antioxidant Nanozyme Activity for Treatment of DSS-Induced Colitis.

Nanozyme-mediated antioxidative therapy is a promising star for treating a myriad of important diseases through eliminating excessive reactive oxygen species (ROS) such as O2·- and H2O2, a critical mechanism for inflammatory bowel disease (IBD). This work provides a high biocompatibility iodine-copper-zinc covalent doped carbon dots (Cu,Zn,I-CDs) with the catalase (CAT)-, superoxide dismutase (SOD)- and glutathione peroxidase (GPx)-like catalytic activities for treating ulcerative colitis (UC) by scavenging overproduced ROS. We found that I dopant aids in counteracting the positive charge at Cu,Zn dopants brought on by low pH, enabling Cu,Zn,I-CDs to process strong triple antioxidant nanozyme activities rather than Cu,Zn-CDs. Vitro experiments displayed that the Cu,Zn,I-CDs could scavenge the excessive ROS to protect cellular against oxidative stress and reduce the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. In sodium dextran sulfate (DSS)-induced colitis mice models, Cu,Zn,I-CDs with excellent biocompatibility could effectively relieve the inflammation of the colon, containing the reduction of the colon length, the damaged epithelium, the infiltration of inflammatory cells, and upregulation of antioxidant genes. Therefore, the therapy of Cu,Zn,I-CD antioxidant nanozymes is an effective approach and provides a novel strategy for UC treatment.

Rapamycin promotes the intestinal barrier repair in ulcerative colitis via the mTOR/PBLD/AMOT signaling pathway

Intestinal barrier dysfunction characterized by the functional loss of the intestinal epithelium's tight junction (TJ) barrier is a key factor in the pathogenesis of ulcerative colitis (UC). Although rapamycin, an mTOR (mechanistic target of rapamycin) inhibitor, has shown promise in inducing clinical remission and mucosal healing in inflammatory bowel disease, its underlying mechanism remains elusive. Thus, this study investigated the role of the mTOR pathway in regulating the intestinal barrier. To investigate the molecular mechanism regulating the intestinal barrier, specific intestinal epithelial phenazine biosynthesis-like domain-containing protein (PBLD)-deficient (PBLDIEC−/−) mice and control wild-type (WT) mice were intraperitoneally injected with rapamycin or MHY1485. To determine the relevance of the findings for UC, we analyzed transcriptome data and single-cell expression profiles from public databases and intestinal mucosal tissues obtained from patients with active UC or colon cancer. We observed that mTOR activation in the intestinal epithelium of patients with active UC. Moreover, in vivo, rapamycin markedly increased the expressions of PBLD and TJ proteins and reduced intestinal inflammation in mice with dextran sulfate sodium-induced enteritis. However, the therapeutic efficacy of rapamycin was notably reduced in PBLDIEC−/− mice. In vitro, rapamycin influenced PBLD expression by modulating the nuclear transcription of transcription factor EB (TFEB). Angiomotin (AMOT) could directly bind to PBLD, and rapamycin could not effectively increase the expression of TJ proteins after the knockdown of PBLD or AMOT. In summary, the administration of rapamycin is a potential treatment for UC, and targeting the mTOR/PBLD/AMOT axis is a potential novel approach for UC treatment.

Ferroptosis: a new mechanism of traditional Chinese medicine for treating ulcerative colitis.

This review summarizes the experimental studies on the targeted regulation of ferroptosis by TCM and its impact on UC in recent years, aiming to provide theoretical basis for the prevention, treatment, and further drug development for UC. Ferroptosis disrupts antioxidant mechanisms in intestinal epithelial cells, damages the intestinal mucosa, and participates in the pathological process of UC. TCM acts on various pathways such as Nrf2/HO-1 and GSH/GPX4, blocking the pathological progression of ferroptosis in intestinal epithelial cells, inhibiting pathological damage to the intestinal mucosa, and thereby alleviating UC. The diverse array of TCM single herbs, extracts and herbal formulas facilitates selective and innovative research and development of new TCM methods for targeting UC treatment. Although progress has been made in studying TCM compound formulas, single herbs, and extracts, there are still many issues in clinical and basic experimental designs, necessitating further in-depth scientific exploration and research.

A molecular subtyping associated with the cGAS-STING pathway provides novel perspectives on the treatment of ulcerative colitis

Ulcerative colitis (UC) is characterized by an abnormal immune response, and the pathogenesis lacks clear understanding. The cGAS-STING pathway is an innate immune signaling pathway that plays a significant role in various pathophysiological processes. However, the role of the cGAS-STING pathway in UC remains largely unclear. In this study, we obtained transcriptome sequencing data from multiple publicly available databases. cGAS-STING related genes were obtained through literature search, and differentially expressed genes (DEGs) were analyzed using R package limma. Hub genes were identified through protein–protein interaction (PPI) network analysis and module construction. The ConsensuClusterPlus package was utilized to identify molecular subtypes based on hub genes. The therapeutic response, immune microenvironment, and biological pathways of subtypes were further investigated. A total of 18 DEGs were found in UC patients. We further identified IFI16, MB21D1 (CGAS), TMEM173 (STING) and TBK1 as the hub genes. These genes are highly expressed in UC. IFI16 exhibited the highest diagnostic value and predictive value for response to anti-TNF therapy. The expression level of IFI16 was higher in non-responders to anti-TNF therapy. Furthermore, a cluster analysis based on genes related to the cGAS-STING pathway revealed that patients with higher gene expression exhibited elevated immune burden and inflammation levels. This study is a pioneering analysis of cGAS-STING pathway-related genes in UC. These findings provide new insights for the diagnosis of UC and the prediction of therapeutic response.