Experimental Model Of Ulcerative Colitis Research Articles

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.

Investigating the effects of combined treatment of mesalazine with Lactobacillus casei in the experimental model of ulcerative colitis.

Ulcerative colitis (UC), a common gastrointestinal disorder in affluent nations, involves chronic intestinal mucosal inflammation. This research investigated the effects of combined probiotic treatment of Lactobacillus casei (L. casei) and mesalazine on disease activity index and inflammatory factors in the UC model. 20 male BALB/c mice were utilized and divided into four groups. To induce UC, all groups received 100 μL of 4% acetic acid (AA) intra-rectally. The first group received phosphate-buffered saline (PBS) (as a control group), the second group was treated with L. casei, the third group was treated with mesalazine and, the fourth group was treated with L. casei and mesalazine. Treatment with L. Casei and mesalazine commenced after the manifestation of symptoms resulting from UC induction. Finally, the mice were euthanized and the disease activity index, myeloperoxidase activity, nitric oxide rate, cytokines level (IL-1β, IL-6, TNF-α) and, gene expression (iNOS, COX-2, and cytokines) were evaluated. The combined treatment of L. casei and mesalazine led to a significant decrease in the levels of NO, MPO and inflammatory cytokines. In addition, the expression of cytokines, iNOS and COX-2 genes decreased in mice treated with the combination. This study shows that combined treatment of L. casei and mesalazine improves of experimental UC, which can be attributed to the anti-inflammatory properties of L. casei and mesalazine. In conclusion, this combination therapy can be considered a suitable option for the management of UC.

Comparing the efficacy of sulfasalazine and an aqueous extract of tarragon in an experimental model of ulcerative colitis

Comparing the efficacy of sulfasalazine and an aqueous extract of tarragon in an experimental model of ulcerative colitis

Anti-inflammatory and anti-hyperalgesic effects induced by an aqueous aged black garlic extract in rodent models of ulcerative colitis and colitis-associated visceral pain.

Inflammatory bowel disease (IBD) is a morbid condition characterized by relapsing-remitting inflammation of the colon, accompanied by persistent gut dysmotility and abdominal pain. Different reports demonstrated biological activities of aged black garlic (ABG), including anti-inflammatory and antioxidant effects. We aimed to investigate beneficial effects exerted by ABGE on colon inflammation by using ex vivo and in vivo experimental models. We investigated the anti-inflammatory effects of an ABG water extract (ABGE) on rat colon specimens exposed to E. coli lipopolysaccharide (LPS), a known ex vivo experimental model of ulcerative colitis. We determined gene expression of various biomarkers involved in inflammation, including interleukin (IL)-1β, IL-6, nuclear factor-kB (NF-kB), tumor necrosis factor (TNF)-α. Moreover, we studied the acute effects of ABGE on visceral pain associated with colitis induced by 2,4-di-nitrobenzene sulfonic acid (DNBS) injection in rats. ABGE suppressed LPS-induced gene expression of IL-1β, IL-6, NF-kB, and TNF-α. In addition, the acute administration of ABGE (0.03-1 g kg-1) dose-dependently relieved post-inflammatory visceral pain, with the higher dose (1 g kg-1) able to significantly reduce both the behavioral nociceptive response and the entity of abdominal contraction (assessed by electromyography) in response to colorectal distension after the acute administration in DNBS-treated rats. Present findings showed that ABGE could represent a potential strategy for treatment of colitis-associated inflammatory process and visceral pain. The beneficial effects induced by the extract could be related to the pattern of polyphenolic composition, with particular regard to gallic acid and catechin.

An insight into the gut microbiota after Schistosoma japonicum eggs immunization in an experimental ulcerative colitis model.

Schistosome infection and schistosome-derived products have been implicated in the prevention and alleviation of inflammatory bowel disease by manipulating the host immune response, whereas the role of gut microbiota in this protective effect remains poorly understood. In this study, we found that the intraperitoneal immunization with Schistosoma japonicum eggs prior to dextran sulfate sodium (DSS) application significantly ameliorated the symptoms of DSS-induced acute colitis, which was characterized by higher body weight, lower disease activity index score and macroscopic inflammatory scores. We demonstrated that the immunomodulatory effects of S. japonicum eggs were accompanied by an influence on gut microbiota composition, abundance, and diversity, which increased the abundance of genus Turicibacter, family Erysipelotrichaceae, phylum Firmicutes, and decreased the abundance of genus Odoribacter, family Marinifilaceae, order Bacteroidales, class Bacteroidia, phylum Bacteroidota. In addition, Lactobacillus was identified as a biomarker that distinguishes healthy control mice from DSS-induced colitis mice. The present study revealed the importance of the gut microbiota in S. japonicum eggs exerting protective effects in an experimental ulcerative colitis (UC) model, providing an alternative strategy for the discovery of UC prevention and treatment drugs.

The Role of Lycium barbarum (Goji Berry) in Apoptosis and Autophagy in the Experimental Ulcerative Colitis Model

The Role of Lycium barbarum (Goji Berry) in Apoptosis and Autophagy in the Experimental Ulcerative Colitis Model

Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis

Ethnopharmacological relevanceBanxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear. Aim of the studyReveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota. Materials and methodsThe major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT). ResultsBXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways. ConclusionBXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.

P079 Low-intensity Pulsed Ultrasound reflects the status of mucosal injury and repair through stage-specific miRNAs in experimental model of Ulcerative Colitis

Abstract Background Diagnosis and therapeutic efficacy monitoring of Ulcerative Colitis (UC) are based on a multidisciplinary approach comprising symptomatology and invasive endoscopic assessment coupled to the histopathological characterization of gut tissue biopsies. New technologies that non-invasively reflect tissue-specific changes remains an unmet need. Here we exploited Low Intensity Pulsed Ultrasound (LIPUS) to induce tissue stage-specific miRNAs in circulating blood as a non-invasive approach to reflect the status of the colonic mucosa in experimental model of colitis. Methods Based on our previous study, LIPUS was applied at a frequency of 38 kHz and at an intensity of 0 (as control) or 150 mW/cm2 for 3 min, using a device dedicated for in vivo studies. Acute and chronic colitis were induced in C57BL/6N mice (5 animals/group) by administration of 2 and 2.5% ad libitum dextran sodium sulfate (DSS) respectively in their drinking water for 7 days for the acute and three cycles of 7 days for the chronic model. miRNA array profiling was performed on extracellular vesicles (EVs) isolated from plasma of both acute and chronic models, at both active and remission state, 2 h after LIPUS stimulation. miRNA were correlated to the mucosal status by multiplexed immunofluorescence staining using Opal Multiplex IHC (CD4, CD8, CD68, pan-cytokeratin and CD31 markers) and EVs characterized by MACSplex surface epitope detection. Results An enrichment of EVs characterized mainly by stromal and immune cell surface markers was found in both acute and chronic inflammatory states, LIPUS stimulation significantly modulated miRNA profiles and clearly discriminated between active acute and chronic phases. 61 miRNAs in acute and 28 in chronic colitis were specifically and significantly upregulated by LIPUS in the active phase, with a fold change ranging from 2 to 1500 compared to control. Both acute and chronic disease showed a miRNA profile coherent with the active inflammatory state of intestinal mucosa. Only 10 and 23 miRNAs were upregulated in acute and chronic remission respectively. The enhancement of miR-18a-3p and miR-301b-3p in the recovery phases correlated to instetin with reduced immune cell infiltration and epithelial layer regeneration. Conclusion An optimal LIPUS dosage that non-invasively targets the colon induces the tissue to release specific miRNAs that reflect the mucosal status. LIPUS may open a new era of non-image ultrasound diagnostics that works as disruptive liquid biopsy allowing the detection of tissue biomarkers for monitoring IBD disease progression.

Evaluation of the Anti-inflammatory Effect of Aqueous Extract of Pistacia atlantica Gum in an Experimental Model of Ulcerative Colitis

Introduction: Ulcerative colitis is a chronic inflammatory bowel disease. Immunosuppressive drugs and various salicylates improve the disease activity index in individuals with ulcerative colitis. Nonetheless, drug resistance and the side effects of these medications drive researchers toward designing studies to find complementary alternatives. Natural compounds, especially derivatives from medicinal plants, hold a special place as supplements. This study aimed to assess the anti-inflammatory effects of the aqueous extract of Pistacia atlantica gum in an experimental model of ulcerative colitis. Materials and Methods: In this study, 20 male BALB/c mice were assigned to four equal groups. The first group served as the healthy control (negative control), the second group represented untreated colitis (positive control), the third group underwent treatment with the aqueous extract of Pistacia atlantica gum, and the fourth group was treated with mesalazine. Ulcerative colitis was induced in all treatment groups except the negative control by using 100 microliters of 4% acetic acid administered intrarectally. The treatment regimen was initiated on the 10th day of post-ulcerative colitis induction and the manifestation of disease symptoms. A week after the final treatment, the mice were euthanized, and various parameters, including levels of myeloperoxidase, nitric oxide, interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and genes, such as iNOS and COX-2, were evaluated. Results: The results indicated that treatment with the aqueous extract of Pistacia atlantica gum significantly decreased the activity of myeloperoxidase (P&lt;0.01), nitric oxide (P&lt;0.05), splenic cell proliferation (P&lt;0.05), expression, and production of inflammatory cytokines, (P&lt;0.05) for IL-1 ß, (P&lt;0.01) for IL-6, and (P&lt;0.01) for TNF-α compared to the positive control group (untreated colitis). Conclusion: As evidenced by the results of this study, it appears that the aqueous extract of Pistacia atlantica gum possesses desirable anti-inflammatory properties that could potentially reduce the disease activity index and inflammatory parameters in the experimental model of ulcerative colitis. Therefore, following further supplementary experiments, it could potentially serve as a complementary therapeutic agent alongside conventional medications for the treatment of patients suffering from ulcerative colitis.

Colo-protective Effect of Grape seed and Flaxseed Oils via Caspase 3 and NF-κB Signaling Inhibition in Experimental Model of Ulcerative Colitis

Colo-protective Effect of Grape seed and Flaxseed Oils via Caspase 3 and NF-κB Signaling Inhibition in Experimental Model of Ulcerative Colitis

Anti-inflammatory activity of peiminine in acetic acid-induced ulcerative colitis model.

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

Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice

Ethnopharmacological relevanceCurrently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear. Aim of the studyThis study is to investigate the protective effects of KJD on UC and the underlying mechanisms. Materials and methodsThe experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry. ResultsMice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism. ConclusionsIn summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC.

Inula viscosa ameliorates acetic acid induced ulcerative colitis in rats

ABSTRACT Increased pro-inflammatory cytokines and oxidative stress contribute to the pathophysiology of ulcerative colitis (UC). Inula viscosa is a plant with antioxidant and anti-inflammatory properties. We investigated the effect of an ethanolic extract of I. viscosa on an experimental UC model created using acetic acid. Rats were divided into four groups of eight: group 1, control; group 2, 3% acetic acid group; group 3, 100 mg/kg sulfasalazine + 3% acetic acid group; group 4, 400 mg/kg I. viscosa + 3% acetic acid. I. viscosa and sulfasalazine were administered by oral gavage and 3% acetic acid was administered per rectum. We found that I. viscosa treatment decreased colon malondialdehyde, tumor necrosis factor-α, interleukin-1 beta and nuclear factor kappa B levels; it increased reduced glutathione, nuclear factor erythroid 2–related factor 2, heme oxygenase-1 and kelch-like ECH-associated protein 1 levels and glutathione peroxidase enzyme activity. Group 1 colon exhibited normal histological structure. Slight inflammatory cell infiltration and edema and insignificant slight erosion in crypts were detected in colon tissues of group 4. We found that I. viscosa reduced oxidative stress and inflammation, which was protective against UC by inducing the Nrf-2/Keap-1/HO-1 pathway in the colon.

Effects of the Antioxidant Quercetin in an Experimental Model of Ulcerative Colitis in Mice.

Background and Objectives: Quercetin, a member of the flavanol family found in many fruits, vegetables, leaves and grains has been found to have a wide range of biological effects on human physiology. The aim of this study was to investigate the effects of quercetin, when administered orally in the form of the water-soluble inclusion complex with hydroxypropyl-b-cyclodextrin (Que-HP-β-CD), in an experimental model of ulcerative colitis in mice. Materials and Methods: Animals received either Dextran Sodium Sulphate (DSS), to induce colitis, + Que-HP-β-CD (Group A), DSS alone (Group B) or no intervention (control, Group C) for 7 days. All animals were weighed daily, and evaluation of colitis was performed using the Disease Activity Index (DAI). On day 7 a blood sample was taken from all animals, they were then euthanised, the large intestine was measured, and histological and immunochemical analyses were performed. Results: The DAI demonstrated an increase over time for the groups receiving DSS (Groups A and B) compared with the control group (Group C), with a significant degree of protection being observed in the group that also received quercetin (Group A): The DAI over time slope for Group B was higher than that for Group A by 0.26 points/day (95% Cl 0.20−0.33, p < 0.01). Weight calculations and immunohistochemistry results validated the DAI findings. Conclusions: In conclusion, the administration of quercetin in an ulcerative colitis model in mice presents a therapeutic/prophylactic potential that warrants further investigation.

Dexmedetomidine alleviates intestinal barrier dysfunction and inflammatory response in mice via suppressing TLR4/MyD88/NF-κB signaling in an experimental model of ulcerative colitis.

Ulcerative colitis (UC) is a nonspecific intestinal inflammatory disease. Dexmedetomidine (DEX) is a selective alpha 2-adrenergic receptor agonist commonly used for analgesia and sedation in intensive care units. Herein, the role and mechanism of DEX in dextran sulfate sodium (DSS)-induced colitis was explored. A murine model of DSS-induced colitis was established by adding 3.5% (w/v) DSS in drinking water to C57BL/6J female mice. The severity of colitis was measured by the disease activity index (DAI) score, colon length and body weight of mice. The serum concentration and mRNA levels of inflammatory cytokines in colon tissues were assessed by ELISA and RT-qPCR, respectively. Protein levels of apoptotic markers, tight junction proteins and genes involved in the TLR4/MyD88/NF-κB signaling were quantified utilizing Western blotting. The pathological changes of colon tissues were evaluated by hematoxylin-eosin (HE) staining and histological score. Intestinal permeability in vivo was assessed by fluorescein isothiocyanate (FITC)-dextran (FITC-D) administration. TUNEL assay was used to determine cell apoptosis in the intestinal epithelium. DSS administration resulted in weight loss, shortening of the colon, increased DAI score, histological abnormalities, and increased serum FITC-D levels in mice, all of which were reversed by DEX injection. Moreover, DEX attenuated DSS-triggered inflammatory response, intestinal barrier injury and intestinal epithelial cell apoptosis. Mechanically, DEX inactivated the TLR4/MyD88/NF-κB signaling in the colon tissues. DEX exerts beneficial effects against the intestinal barrier dysfunction, inflammatory response, and apoptosis of intestinal epithelial cells via inactivation of the TLR4/MyD88/NF-κB signaling in mice with DSS-induced colitis.

Anti-Inflammatory and Antioxidant Effects Induced by Allium sativum L. Extracts on an Ex Vivo Experimental Model of Ulcerative Colitis.

Inflammatory bowel diseases (IBDs) are chronic and multifactorial inflammatory conditions of the colonic mucosa (ulcerative colitis), characterized by increased and unbalanced immune response to external stimuli. Garlic and its bioactive constituents were reported to exert various biological effects, including anti-inflammatory, antioxidant and immunomodulatory activities. We aimed to evaluate the protective effects of a hydroalcoholic (GHE) and a water (GWE) extract from a Sicilian variety of garlic, known as Nubia red garlic, on an ex vivo experimental model of ulcerative colitis, involving isolated LPS-treated mouse colon specimens. Both extracts were able to counteract LPS-induced cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, nuclear factor-kB (NF-kB), and interleukin (IL)-6 gene expression in mouse colon. Moreover, the same extracts inhibited prostaglandin (PG)E2, 8-iso-PGF2α, and increased the 5-hydroxyindoleacetic acid/serotonin ratio following treatment with LPS. In particular, GHE showed a better anti-inflammatory profile. The anti-inflammatory and antioxidant effects induced by both extracts could be related, at least partially, to their polyphenolic composition, with particular regards to catechin. Concluding, our results showed that GHE and GWE exhibited protective effects in colon, thus suggesting their potential use in the prevention and management of ulcerative colitis.

Curcumin-Loaded Microspheres Are Effective in Preventing Oxidative Stress and Intestinal Inflammatory Abnormalities in Experimental Ulcerative Colitis in Rats.

Curcumin’s role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples’ collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

Construction, bioinformatics analysis, and validation of competitive endogenous RNA networks in ulcerative colitis.

Background: Ulcerative colitis (UC) is a common chronic disease of the digestive system. Recently, competitive endogenous RNAs (ceRNAs) have been increasingly used to reveal key mechanisms for the pathogenesis and treatment of UC. However, the role of ceRNA in UC pathogenesis has not been fully clarified. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA ceRNA network in UC and identify potential biomarkers and therapeutic targets. Materials and Methods: An integrative analysis of mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA) files downloaded from the Gene Expression Omnibus (GEO) was performed. Differentially expressed mRNA (DE-mRNAs), miRNA (DE-miRNAs), and lncRNA (DE-lncRNAs) were investigated between the normal and UC groups by the limma package. A weighted correlation network analysis (WGCNA) was used to identify the relative model for constructing the ceRNA network, and, concurrently, miRWalk and DIANA-LncBase databases were used for target prediction. Consecutively, the Gene Ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway, and Reactome pathway enrichment analyses, protein-protein interaction (PPI) network, Cytohubba, and ClueGO were performed to identify hub genes. Additionally, we examined the immune infiltration characteristics of UC and the correlation between hub genes and immune cells using the immuCellAI database. Finally, the expression of potential biomarkers of ceRNA was validated via qRT-PCR in an experimental UC model induced by dextran sulfate sodium (DSS). Result: The ceRNA network was constructed by combining four mRNAs, two miRNAs, and two lncRNAs, and the receiver operating characteristic (ROC) analysis showed that two mRNAs (CTLA4 and STAT1) had high diagnostic accuracy (area under the curve [AUC] > 0.9). Furthermore, CTLA4 up-regulation was positively correlated with the infiltration of immune cells. Finally, as a result of this DSS-induced experimental UC model, CTLA4, MIAT, and several associate genes expression were consistent with the results of previous bioinformatics analysis, which proved our hypothesis. Conclusion: The investigation of the ceRNA network in this study could provide insight into UC pathogenesis. CTLA4, which has immune-related properties, can be a potential biomarker in UC, and MIAT/miR-422a/CTLA4 ceRNA networks may play important roles in UC.

Efficacy of Sishen Wan on dinitrobenzene sulfonic acid-induced ulcerative colitis and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB signal pathway.

To investigate the therapeutic effect of Sishen Wan (, SSW) on ulcerative colitis (UC) induced by dinitrobenzene sulfonic acid and its effect on toll-like receptor 2/interleukin-1 receptor-associated kinase-4/nuclear factor-κB (TLR2/IRAK4/NF-κB) sig-naling pathway in colonic tissue. In this study, 120 Sprague-Dawley rats were randomly divided into blank and model groups. The experimental UC model in rats was established by subcutaneous injection of hydrocortisone + senna gavage for 21 d + dinitrobenzene sulfonic acid (DNBS)/ ethanol solution enema. The successful model rats were randomly divided into the model group; mesalazine (0.36 g/kg) group; and high-, medium-, and low- dose SSW (24, 12, and 6 g/kg) groups. The model and blank groups were gavaged with equal volumes of distilled water once a day for 21 d. The general condition of the rats was observed, and the body mass, fecal properties, and occult blood were recorded for calculating the disease activity index (DAI) score. The colonic tissue of the rats was collected, and its general morphology and pathological form were noted for obtaining the colonic mucosal injury index (CMDI) score. Hematoxylin-eosin staining was used to view the pathological changes of the colon tissue in each group, apoptosis of the cells was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and quantitative real-time polymerase chain reaction was used to measure the expressions of TLR2, myeloid differentiation primary response gene 88 (MyD88), IRAK4, and NF-κB p65 mRNA in the colon tissue. The expressions of TLR2, MyD88, IRAK4, and NF-κB p65 protein were detected using western blotting and immunohistochemistry assay, and the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the colon tissue were determined using enzyme linked immunosorbent assay. Compared with the blank group, the general condition of the model group was relatively poor. The DAI and CMDI scores of the model group increased significantly (< 0.01), the glands and intestinal mucosa disappeared partially, and several inflammatory cells infiltrated and gathered in the mucosal layer and base layer of the rats in the model group. Furthermore, the cell apoptosis and expression levels of TLR2, MyD88, IRAK4, and NF-κB p65 mRNA and protein in the colon tissue of rats in the model group increased significantly (< 0.01). The levels of IL-1β and TNF-α increased significantly in the colon tissue of rats in the model group (< 0.01). After treatment with SSW, compared with the model group, the general condition of the UC rats improved. Moreover, the DAI and CMDI scores of the UC rats decreased significantly (< 0.05), and the pathological changes in the colon tissue of the UC rats tended to be normal. The cell apoptosis and expression levels of TLR2, MyD88, IRAK4, and NF-κB p65 mRNA and protein in the colon tissue of the UC rats decreased gradually ( < 0.01), and the levels of IL-1β and TNF-α decreased significantly (< 0.01). SSW can improve the general condition and alleviate the intestinal mucosal injury of UC model rats. Additionally, SSW can inhibit the TLR2/IRAK4/ NF-κB signaling pathway, but further studies are required to confirm it.

Preclinical studies of licorice in ulcerative colitis: A systematic review with meta-analysis and network pharmacology

Ethnopharmacological relevanceLicorice, as a traditional Chinese herbal medicine, possessing the efficacies of invigorating spleen and replenishing qi, heat-clearing and detoxicating, phlegm-resolving and cough suppressant, relieving spasm and pain, and hamonizing actions of various medicines. Aim of the studyThe goal of this systematic review, which includes meta-analysis and network pharmacology in preclinical studies, is to investigate the multiple efficacies of licorice on ulcerative colitis (UC). Materials and methodsWe searched several databases, e.g., Web of Science, Elsevier ScienceDirect and PubMed until Januanry 2022 for literature collection, and the Review Manager 5.3 was used to analyze the data. To synthesize the retrieved data, the fixed and random-effects models were utilized, respectively, and network pharmacology was applied to confirm the mechanisms. ResultsBased on the result of meta-analysis, it suggested that the treatments of licorice extract and its active compounds showed strong therpeutic effects, which not only reflected the declining histological score, a index of the colitis severity [SMD = −2.86, 95% CI (−3.65, −2.08); P < 0.00001], but also reversed colonic shortness [WMD = 1.67, 95% CI (1.16, 2.19); P < 0.00001] between experimental UC model and licorice-treatment groups. In addition, it suggested the significant reduction of TNF-α level [SMD = −2.70, 95% CI (−3.23, −2.16); P < 0.00001], which acted as a crucial role in inflammatory response. Furthermore, from the results of network pharmacology, it indicated that anti-inflammation, anti-oxidative stress, immunomodulatory effect and microbiota homeostasis were the predominant therapeutic mechanisms of licorice extract and its active compounds treating UC. ConclusionThis systematic review with meta-analysis and network pharmacology demonstrates an efficient role of licorice extract and its active compounds in preclinical studies of UC, which provides supporting evidence for clinical trial implementation. However, there exist some limitations, such as technique quality decificency, missed reports due to negative outcome, failure to calculate sample size, and the risk of bias.