Ulcerative Colitis In Rats Research Articles

Mesalazine hollow suppositories based on 3D printing for treatment of ulcerative colitis

Mesalazine (MSZ) suppositories are a first-line medication for the localized treatment of ulcerative colitis (UC). However, the frequent defecation of patients with UC influences the retention of the suppository in the rectum and multiple doses have to be applied. Here, a mesalazine hollow suppository (MHS) is developed using three-dimensional (3D) printing. The MHS is composed of an inner supporting spring and an outer MSZ-loaded curved hollow shell. Springs were prepared using fused deposition modeling (FDM) 3D printing with thermoplastic urethane filaments, followed by splitting. The optimal parameters, including elasticity, filament diameter, spring inner diameter, and filament distance, were screened. The shell was prepared by FDM 3D printing utilizing MSZ, polyvinyl alcohol, and polyethylene glycol, which were assembled with springs to obtain FDM 3D-printed MHS (F-MHS); if 3D-printed metal molding was used in preparing shell, mold-formed MHS (M-MHS) was obtained. The F-MHS exhibited faster MSZ release than the M-MHS; therefore, the molding method is preferable. The inserted M-MHS was retained in the rat rectum for 5 h without affecting defecation. M-MHS alleviated tissue damage of UC rats and reduced inflammation with low levels of myeloperoxidase and proinflammatory cytokines. Personalized MHS is a promising medication for the localized treatment of UC.

Morphological, Biochemical and Molecular Docking Evaluation of the Anti-inflammatory Effects of Methanolic Extract of Bridelia ferruginea stem bark on Acetic acid-induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is a chronic disorder that involves inflammation. This study was carried out to examine the anti-inflammatory effect of the methanol extract of Brideliaferrugineastem barkinAcetic acid-induced ulcerative colitis inmaleWistarrats. Twenty-four rats were randomly divided into 6 groups of 4 animals each, colitis was thereafter induced by intrarectal administration of4% (v/v)Aceticacidin all except group 1, which received distilled water. For post-colitis induction treatment group 2 received distilled water, groups 3, 4 and 5 were orally administeredthe extract at doses of 100mg/kg, 200mg/kg and 400mg/kg, respectively while group 6 received sulfasalazine 500mg/kg orally.Post colitis induction, treatment lasted for 7 days and at the end of the experiment, colon samples were collected for estimation of antioxidant, inflammatory and histological parameters. Molecular docking study was also carried out to gain more insights about the promising anti-inflammatory compounds earlier identified in the extract.Results revealed that the extract significantly (p<0.05) attenuated the increased MDA, nitrite,TNF-α and IL-6 levels. Activities of SOD, CAT, MPO and GSH levelswere also, significantly (p<0.05) increased. Furthermore, molecular docking study revealed that α-amyrin may have contributed significantly to the anti-inflammatory activity of the extract because of its remarkable binding affinity for IL-6, iNOS, IL1-β,TNF-α and COX-2 relative to prednisolone and celecoxib. This study suggests that the extract attenuated acetic acid-induced colitis via antioxidative and anti-inflammatory mechanisms. .

Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis.

This study aimed to investigate the effect of oleracein E (OE) in improving 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC). Lipopolysaccharide (LPS) was used to induce a UC cell model, and TNBS was used to induce a UC rat model. ELISA was performed to assess the levels of inflammatory factors (IL-1β, TNF-α, and IL-6). Moreover, the activities of catalase (CAT), myeloperoxidase (MPO), and malonaldehyde (MDA) were detected by kits. Western blotting was performed to assess related proteins of the Nrf2/HO-1 signaling pathway, tight junction protein (ZO-1, Occludin, and claudin-2) expression levels, and apoptosis-related proteins (Bcl2, Bax, and cleaved caspase 3). Flow cytometry was used to analyze ROS levels. The morphology of colon tissues and the apoptosis of cells were detected by HE and TUNEL staining, respectively. OE significantly increased the activity of CAT and decreased the activity of MPO in LPS-induced Caco-2 cells and TNBS-induced UC rats. However, the levels of IL-1β, IL-6, and TNF-α were markedly reduced both in vivo and in vitro. In addition, OE significantly increased the levels of Nrf2/HO-1 signaling pathway-related proteins and tight junction proteins and inhibited cell apoptosis. HE staining showed that OE significantly decreased the severity of acute TNBS-induced colitis in rats. OE may exert a regulatory effect on ameliorating intestinal barrier injury and reducing inflammation and oxidative stress levels by activating the Nrf2/HO-1 pathway.

The immunomodulatory effects of probiotics and azithromycin in dextran sodium sulfate-induced ulcerative colitis in rats via TLR4-NF-κB and p38-MAPK pathway

Ulcerative colitis (UC), a chronic autoimmune disease of the gut with a relapsing and remitting nature, considers a major health-care problem. DSS is a well-studied pharmacologically-induced model for UC. Toll-Like Receptor 4 (TLR4) and its close association with p-38-Mitogen-Activated Protein Kinase (p-38 MAPK) and nuclear factor kappa B (NF-κB) has important regulatory roles in inflammation and developing UC. Probiotics are gaining popularity for their potential in UC therapy. The immunomodulatory and anti-inflammatory role of azithromycin in UC remains a knowledge need. In the present rats-established UC, the therapeutic roles of oral probiotics (60 billion probiotic bacteria per kg per day) and azithromycin (40 mg per kg per day) regimens were evaluated by measuring changes in disease activity index, macroscopic damage index, oxidative stress markers, TLR4, p-38 MAPK, NF-κB signaling pathway in addition to their molecular downstream; tumor necrosis factor alpha (TNFα), interleukin (IL)1β, IL6, IL10 and inducible nitric oxide synthase (iNOS). After individual and combination therapy with probiotics and azithromycin regimens, the histological architecture of the UC improved with restoration of intestinal tissue normal architecture. These findings were consistent with the histopathological score of colon tissues. Each separate regimen lowered the remarkable TLR4, p-38 MAPK, iNOS, NF-κB as well as TNFα, IL1β, IL6 and MDA expressions and elevated the low IL10, glutathione and superoxide dismutase expressions in UC tissues. The combination regimen possesses the most synergistic beneficial effects in UC that, following thorough research, should be incorporated into the therapeutic approach in UC to boost the patients’ quality of life.

Therapeutic effect of Yiyi Fuzi Baijiang formula on TNBS-induced ulcerative colitis via metabolism and Th17/Treg cell balance.

Yiyi Fuzi Baijiang formula (YFB) is a traditional Chinese medicine prescription composed of Coix seed, Radix Aconiti Lateralis and Patrinia villosa, which has been used to treat ulcerative colitis (UC) for thousands of years. To investigate the therapeutic effect and metabolic analysis of YFB formula on UC in rats induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS). Six main alkaloids in the YFB formula were determined by UPLC‒MS/MS. The rat UC model was induced by TNBS, and the therapeutic effect of YFB formula on UC was evaluated by disease activity index (DAI) score and hematoxylin-eosin (HE) staining. UPLC-QTRAP-MS metabolomics technology was used to screen potential biomarkers for YFB treatment of UC in combination with multivariate data statistics and further analyze related metabolic pathways. Western blotting was used to detect the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in rat liver tissues. ELISA and immunohistochemistry were used to detect the contents of interleukin (IL)-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in rat serum and liver tissues. The DAI scores of the YFB groups were significantly reduced, and colon tissue injury was significantly improved (p<0.01). The results of metabolomics analysis revealed 29 potential biomarkers in serum and 27 potential biomarkers in liver. YFB formula can treat UC by affecting glycerophospholipid metabolism, primary bile acid biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, and arginine and proline metabolism. Compared with the model group, the contents of IL-17A, IL-21, IL-22, IL-6, TNF-α, IL-1β and IL-18 in the YFB groups were decreased in a dose-dependent manner (p<0.01). Compared with those in the model group, the protein levels of NLRP1, NLRP3, NLRC4, ASC, pro-caspase1 and Caspase-1 in the YFB groups were significantly decreased in a dose-dependent manner (p<0.01). The therapeutic effect of YFB formula on UC rats was dose dependent, and the effect of the YFB (2.046g/kg) group was close to that of the positive group. YFB formula has an anti-inflammatory effect on UC by regulating the balance of Th17/Treg cells in rats.

Ameliorative effect of aqueous extract of Carica papaya Linn. leaves on Acetic acid induced Ulcerative Colitis in Male Albino Wistar rats

Ulcerative colitis (UC) manifests as chronic inflammation of the colon. The bowel inflammation is due to alteration in the immune response to gut micro flora, oxidative stress and hereditary genetic factors. Leaf extract of papaya Carica papaya Linn. contain vitamin A, C, alkaloids, saponins, glycosides, tannins and flavonoids which have antispasmodic, analgesic, antibacterial and antioxidant properties. The main aim of the study was to detect the efficacy of Carica papaya leaf extract (PLE) on ulcerative colitis in Wistar Albino rats with objectives to explore the possible mechanism involved in its efficacy and to look for prebiotic activity. The project was initiated after the approval of Institutional Animal Ethics Committee. Thirty adult Wistar rats were randomly assigned into seven groups of six rats each. Group I-control, Group II-UC disease control, Group III-Disease with standard Sulfasalazine 100mg/kg, Group IV and Group V, UC disease model receiving PLE of 250mg/kg and 500 mg/kg respectively. Ulcerative colitis was not induced in Group VI and Group VII which received PLE of 500mg/kg and 700 mg/kg respectively. All the drugs were administered orally for 15 days. UC was induced by acetic acid on the 8th day. Blood sample was collected for biochemical analysis for antioxidant levels. Histopathological analysis of distal colon was performed to look for inflammatory features. Microbial analysis was done for group VI and group VII. There was significant reduction in body weight in UC induced groups when compared to control. The weight loss in Group IV and V (PE1 and PE2) was not as extreme as seen in the UC alone group. The treatment groups IV and V showed significant increase in protein levels, increased catalase and decreased malondialdehyde levels when compared to Group I, II and III. On histopathological analysis, the severity and extent of inflammation was less in 500mg/kg dose of leaf extract (Group V) than 250mg/kg of leaf extract (Group IV) and 100mg/kg of sulfasalazine (Group III). Tissue sections of Group V showed only few inflammatory infiltrates with absence of oedema and crypt abscess in the submucosal area. On examining the pathogenic versus beneficial bacterial load in the control and Group VI (PE 3) and Group VII (PE 4), papaya leaf extracts depicted antibacterial property and probiotic activity. In the present study, 500mg/kg of papaya leaf extract was efficacious in relieving oxidative stress and reducing inflammation in acetic acid induced ulcerative colitis in rats. Carica papaya leaf extracts have a potential role to modify gut microbe with respect to its prebiotic activity.

The coumaric acid and syringic acid ameliorate acetic acid-induced ulcerative colitis in rats via modulator of Nrf2/HO-1 and pro-inflammatory cytokines

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes uncontrolled inflammation and ulcers in your digestive tract. The coumaric acid and syringic acid are phenolic derivative found in many fruits and vegetables and is widely recognized for the ability of anti-parasitic, anti-microbial, anti-viral, anti-inflammatory, and antioxidant. The purpose of this study was to investigate the anti-inflammatory and antioxidant properties of coumaric acid and syringic acid on acetic acid-induced colitis in rats. MethodsA total of 64 male Wistar rats were divided into eight equal groups (n = 8). Colitis was induced by intrarectal administration of acetic acid, and rats orally received coumaric acid (100 and 150 mg/kg), syringic acid (10, 25, and 50 mg/kg), and dexamethasone (2 mg/kg) once per day for four days after colitis induction. Then, HO-1, Nrf2, and NQO1 mRNA expression were quantified by real time-PCR. Finally, the tissue levels of TNF-α and IL-1β protein were measured by ELISA. ResultsColitis led to a decrease in HO-1, Nrf2, and NQO1 mRNA expression and an increase in the tissue levels of TNF-α and IL-1β protein in the colon tissue. Treatment with dexamethasone significantly increased HO-1, Nrf2, and NQO1 mRNA expression and decreased the tissue levels of TNF-α and IL-1β protein compared to the UC group. Treatment with 150 mg/kg of coumaric acid and 50 mg/kg of syringic acid significantly increased HO-1, Nrf2, and NQO1 mRNA expression compared to the UC group. Also, treatment with 100 and 150 mg/kg of coumaric acid and 10, 25, and 50 mg/kg of syringic acid significantly decreased the tissue levels of TNF-α and IL-1β protein compared to the UC group. ConclusionThe coumaric acid and syringic acid, especially at high doses, may be an alternative strategy for the treatment of UC by the reduction of TNF-α and IL-1β levels and upregulation of the Nrf2/HO-1 pathway.

Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis.

Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1β, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1β, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1β, IL-6 and TNF-α levels. PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis.

Long Non-Coding RNAs Nuclear Paraspeckle Assembly Transcript 1 Antagonist Encapsulated by Liposome Nanoparticles Regulates Macrophage Glucose Metabolism Reprogramming in Ulcerative Colitis

This study explored the mechanism by which Long Non-Coding RNA-Nuclear Enriched Abundant Transcript 1 (LncRNA-NEAT1) antagonists encapsulated in liposome nanoparticles regulate reprogramming of macrophage glucose metabolism in ulcerative colitis (UC) patients. Sprague-Dawley (SD) rats were assigned into blank control group, UC model group, LncRNA-NEAT1 antagonist group (antagonist group) and LncRNA-NEAT1 antagonist encapsulated by liposome nanoparticles group (nano+antagonist group). Rats in the blank control group were not given any intervention, while rats in the UC model group were fully anesthetized to establish a UC model. The antagonist group was given LncRNA-NEAT1 antagonists on the basis of the UC model. Combined intervention with LncRNA-NEAT1 antagonists encapsulated by plastid nanoparticles were given to the nano+antagonist group. LncRNA-NEAT1 antagonist encapsulated by liposome nanoparticles reduced colon mucosal damage index and CMDI) score of UC rats, improving gross morphology damage of mucosa, and also reducing the pathological damage of lung tissue in the rats. The LncRNA-NEAT1 antagonist inhibited reprogramming level of glucose metabolism in macrophages, reduced consumption of cellular glucose, and further reduced lactic acid content in the macrophages. In addition, the LncRNA-NEAT1 antagonist further inhibited the expression of glycolysis-related enzymes in macrophages by inhibiting Rho associated coiled-coil containing protein kinase/Myosin streptophilic kinase (ROCK/MLCK) pathway. LncRNA-NEAT1 has a targeting relationship with ROCK/MLCK pathway. In conclusion, down-regulating NEAT1 inhibited the activity of ROCK/MLCK signaling, reducing inflammatory response, thereby repairing the intestinal barrier function, and inhibiting the reprogramming of glucose metabolism in macrophages from the UC rats. In addition, liposome nanoparticle encapsulation has broad prospects in the field of drug delivery, which can achieve the purpose of enhancing drug efficacy.

Echinacea purpurea (L.) Moench extract suppresses inflammation by inhibition of C3a/C3aR signaling pathway in TNBS-induced ulcerative colitis rats.

Echinacea purpurea (L.) Moench (EP) is a perennial herbaceous flowering plant, commonly known as purple conical flower. It was widely used to treat skin inflammation and gastrointestinal diseases. Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease. Recent evidence shows that immune disorders are involved in the pathogenesis of UC. To evaluate the protective effect of Echinacea purpurea (L.) Moench exact (EE) on UC and explore the role of complement system in the treatment of UC. UC model was induced in rats by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and then rats were administered with EE for 10 days. Collect colon tissues for analysis of relevant mechanisms. EE could reduce the weight loss and diarrhea of UC rats. In addition, EE could improve the integrity of intestinal epithelial barrier in UC rats. EE inhibited the level of proinflammatory cytokines and promoted the antioxidation. Furthermore, EE suppressed the expression of C3aR, CFB, CD55, TLR4 and NLRP3. These results indicate that EE may achieve therapeutic effect by inhibiting C3a/C3aR signal pathway, suggesting that EE may be used as a medicinal plant to alleviate UC.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60–70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4–0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon’s tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.

Therapeutic effects of genistein in experimentally induced ulcerative colitis in rats via affecting mitochondrial biogenesis.

Ulcerative colitis (UC) is an inflammatory bowel disease that affects the mucosa of the colon, resulting in severe inflammation and ulcers. Genistein isa polyphenolic isoflavone present in several vegetables, such as soybeans and fava beans. Therefore, we conducted the following study to determine the therapeutic effects of genistein on UC in rats by influencing antioxidant activity and mitochondrial biogenesis and the subsequent effects on the apoptotic pathway. UC was induced in rats by single intracolonic administration of 2ml of 4% acetic acid. Then, UC rats were treated with 25-mg/kg genistein. Colon samples were obtained to assess the gene and protein expression of nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1), mitochondrial transcription factor A (TFAM), B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), caspase-3, caspase-8, and caspase-9. In addition, colon sections were stained with hematoxylin/eosin to investigate the cell structure. The microimages of UC rats revealed inflammatory cell infiltration, hemorrhage, and the destruction of intestinal glands, and these effects were improved by treatment with genistein. Finally, treatment with genistein significantly increased the expression of PGC-1, TFAM, Nrf2, HO-1, and BCL2 and reduced the expression of BAX, caspase-3, caspase-8, and caspase-9. In conclusion, genistein exerted therapeutic effects against UC in rats. This therapeutic activity involved enhancing antioxidant activity and increasing mitochondrial biogenesis, which reduced cell apoptosis.

Microbiome-Metabolomics Analysis Reveals the Mechanism of Holothuria leucospilota Polysaccharides (HLP) in Ulcerative Colitis.

Holothuria leucospilota polysaccharides (HLP) are bioactive polysaccharides with immunomodulatory effects. This study aims to investigate the impact of HLP on dextran sodium sulfate (DSS)-induced colitis in rats and further investigate the complex interactions between changes in intestinal microbiota, cometabolites, and intestinal inflammation under HLP intervention. The ulcerative colitis (UC) model of Sprague Dawley (SD) rats is established by a normal diet with 3%DSS. The effects of HLP on UC are studied by gavage of different doses of HLP for 2weeks. The results show that HLP alleviate the inflammation of UC and reduce histological damage and secretion of tumor necrosis factor-α (TNF-α), IL-6, IL-1β, and IL-10. After HLP treatment, the intestinal flora of UC rats is regulated, and the flora diversity is restored. Fecal metabolomics analysis reveal the modulatory effects of HLP on amino acid metabolism, antimicrobial peptide anabolism, and energy metabolism in rats with colitis. Correlation analysis of microbial and intestinal metabolites reveals the potential mechanism of HLP affecting colitis. HLP repair the intestinal compartment's metabolic disorder by regulating intestinal flora's structure and alleviating colonic mucosal injury and inflammation in colitis rats.

Preparation of baicalin colon-targeted granules and its intervention effect on ulcerative colitis in rats

Baicalin (BA) is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological activities. In this study, Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules (EBCGs) based on plasticizer dry powder coating technology to improve the targeting transportation performance of BA. In vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating, and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract (GIT). In vivo studies showed that EBCGs had good therapeutic effects in colitis, which reduced expression levels of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) and increased superoxide dismutase (SOD) activities in the colonic tissues of rats with colitis. In conclusion, Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology, and our prepared EBCGs had good colon-targeting properties, which could improve the therapeutic effect and provide a potential application for ulcerative colitis (UC).

Efficacy of Qifu Lizhong enema prescription on intestinal mucosal tight junction function modulation of ulcerative colitis rat model.

To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(, QFLZ) on intervening ulcerative colitis (UC) rat model with TCM spleen and kidney insufficiency syndrome. Seventy-two male Sprague-Dawley rats were randomly assigned to six groups: normal model, mesalazine, and QFLZ high, medium, and low dose groups, each with 12 rats. After 3 d of adaptation feeding, all groups except the normal group were induced using rhubarb decoction in combination with trinitrobenzene sulfonic acid (TNBS)/55 % ethanol to establish a UC rat model. Following successful modeling, the normal and model groups received daily saline enema, while the Chinese medicine and Western medicine groups received daily QFLZ and Mesalazine enema for 2 weeks respectively. The disease activity index score, hematoxylin and eosin staining, immunohistochemistry, and Western blotting were used to determine the expression of claudin 1, claudin 2, zonula occludens-1 protein (ZO-1), and F-actin proteins in each rat colon tissue following treatment. QFLZ significantly alleviated the structural disorganization in the form of epithelial glands in the intestinal mucosa of rats with UC and retarded the progression of the disease. The intestinal mucosal epithelial cells of UC rats showed decreased expression of claudin 1, ZO-1, F-actin ( 0.05), claudin 2 appeared elevated ( 0.05), which resulted in impaired TJ. Treatment with QFLZ resulted in elevated expression of claudin 1 ( 0.05), ZO-1 ( 0.05) and F-actin ( 0.05) and decreased expression of claudin 2 ( 0.05), which allowed for repair of the intestinal mucosal TJ, which in turn served as a treatment for UC. The mechanism of repairing TJ function and repairing the intestinal mucosal barrier by QFLZ may be associated with up-regulation of claudin 1, ZO-1, and F-actin levels, and down-regulation of claudin 2 expression level.

Wei Chang An pill alleviates 2,4,6-trinitro-benzenesulfonic acid-induced ulcerative colitis by inhibiting epithelial-mesenchymal transition process

Objective: To investigate the inhibitory effect and mechanism of Wei Chang An pill (WCA) on ulcerative colitis (UC). Methods: A TNBS-induced UC model was established, and WCA was administered orally for one week. Body weight, colon length, disease activity index (DAI) score, and colon mucosa damage index (CMDI) score were recorded. Cytokine expression in lipopolysaccharide (LPS)-stimulated THP-1 cells was evaluated to determine the anti-inflammatory effects of WCA and its active ingredients. Immunohistochemistry and immunofluorescence were performed to detect the expression of epithelial-mesenchymal transition (EMT) markers E-cadherin and vimentin in rat UC and WCA groups, and in Caco-2 cells stimulated with conditioned medium (CM) from THP-1 cells, with or without LPS or WCA. Results: WCA significantly inhibited body weight loss, decreased DAI and CMDI scores, blocked colon length shortening, and improved histological damage in UC rats. Furthermore, both myeloperoxidase (MPO) activities and cytokine expression in UC tissues were significantly suppressed by WCA as well. In THP-1 cells, the mRNA expression of interferon-inducible protein (IP)-10, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and NF-κB inhibitor α (IkBα) was significantly suppressed by WCA and its active ingredients. E-cadherin expression in UC rats and CM-stimulated Caco-2 cells was downregulated and vimentin expression was upregulated, whereas both were blocked when administered with WCA. Conclusion: Our data showed that WCA alleviated UC progression by inhibiting inflammation-induced EMT progression.

Cotinus coggygria Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators.

In traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.

Banxia Xiexin decoction ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis via inhibiting serine-threonine protein kinase (Akt)/mitogen-activated protein kinase (MAPK) signaling pathway.

Banxia Xiexin decoction (BXD), a traditional Chinese medicine, was widely used in treating ulcerative colitis (UC). However, the active components of BXD and its mechanism in UC remain elusive. Therefore, we used network pharmacology in vivo experiments, molecular docking, and surface plasmon resonance strategy (SPR) to uncover BXD's potential mechanism. A UC rat model was established by orally administering 7% dextran sulfate sodium (DSS) in drinking water, BXD and palmatine were orally administered for 7days. Network pharmacology was used to investigate the main bioactive components and crucial targets of BXD in treating UC. Molecular docking was used to investigate interactions between components and crucial targets, verifying the results by SPR. By network pharmacology predicting, 20 active components and 44 candidate anti-UC targets of BXD were identified, and the crucial proteins were screeded from PPI network, including extracellular regulated protein kinases (ERK), AKT1, and tumor necrosis factor-α (TNF). In addition, some key active components (palmatine, sexangularetin, and skullcapflavone II) were screened out from the active components-targets network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and in vivo experiments showed that protein-serine-threonine kinase (Akt)/MAPK pathway was involved in BXD treatment for UC; BXD and palmatine significantly ameliorated the severity of DSS-induced UC in rats. Our study might assist in further investigation of the active components in Chinese medicine.

Ezetimibe alleviates acetic acid-induced ulcerative colitis in rats: targeting the Akt/NF-κB/STAT3/CXCL10 signaling axis.

Ulcerative colitis (UC) is a relapsing inflammatory health state posing significant worldwide problems. Ezetimibe is a cholesterol-lowering drug having anti-inflammatory and pleiotropic properties. Twenty-four rats were classified into four groups (n = 6). Group (I) was considered negative control. Acetic acid (AA) was instilled intrarectally in groups (II-IV). Group (II) was considered UC-control. Groups (III and IV) were orally treated with Ezetimibe (5 and 10 mg/kg/day; 14 days). AA installation resulted in severe macroscopic colonic lesions associated with elevations in the relative colon weight, the wet weight/length ratio and oxidative stress markers in the colorectum tissues. UC-control rats showed significantly elevated colorectal tissue CXCL10 and STAT3 gene expression. Akt, phosphorylated Akt, phosphorylated STAT3, TNF-α, IL-6 and NF-κB were expressively upregulated in the UC-control group. AA installation also resulted in significant histopathological alterations in the colorectum tissues of UC-control rats along with increasing the colorectal tissues' immunohistochemical iNOS expression. Collectively, these data suggest activation of the Akt/NF-κB/STAT3/CXCL10 signaling axis. Ezetimibe treatment significantly ameliorated all the aforementioned parameters. This is the first study to elucidate the modulatory actions of Ezetimibe against oxidative stress and inflammation associated with AA-induced UC in rats. Ezetimibe treatment mitigates UC via downregulation of the Akt/NF-κB/STAT3/CXCL10 signaling axis.

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.