Ulcerative Colitis In Rats Research Articles

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.

A novel oral formulation of the melanocortin-1 receptor agonist PL8177 resolves inflammation in preclinical studies of inflammatory bowel disease and is gut restricted in rats, dogs, and humans.

PL8177 is a potent and selective agonist of the melanocortin 1 receptor (MC1R). PL8177 has shown efficacy in reversing intestinal inflammation in a cannulated rat ulcerative colitis model. To facilitate oral delivery, a novel, polymer-encapsulated formulation of PL8177 was developed. This formulation was tested in 2 rat ulcerative colitis models and evaluated for distribution, in vivo, in rats, dogs, and humans. The rat models of colitis were induced by treatment with 2,4-dinitrobenzenesulfonic acid or dextran sulfate sodium. Single nuclei RNA sequencing of colon tissues was performed to characterize the mechanism of action. The distribution and concentration of PL8177 and the main metabolite within the GI tract after a single oral dose of PL8177 was investigated in rats and dogs. A phase 0 clinical study using a single microdose (70 µg) of [14C]-labeled PL8177 investigated the release of PL8177 in the colon of healthy men after oral administration. Rats treated with 50 µg oral PL8177 demonstrated significantly lower macroscopic colon damage scores and improvement in colon weight, stool consistency, and fecal occult blood vs the vehicle without active drug. Histopathology analysis resulted in the maintenance of intact colon structure and barrier, reduced immune cell infiltration, and increased enterocytes with PL8177 treatment. Transcriptome data show that oral PL8177 50 µg treatment causes relative cell populations and key gene expressions levels to move closer to healthy controls. Compared with vehicle, treated colon samples show negative enrichment of immune marker genes and diverse immune-related pathways. In rats and dogs, orally administered PL8177 was detected at higher amounts in the colon vs upper GI tract. [14C]-PL8177 and the main metabolite were detected in the feces but not in the plasma and urine in humans. This suggests that the parent drug [14C]-PL8177 was released from the polymer formulation and metabolized within the GI tract, where it would be expected to exert its effect. Collectively, these findings support further research into the oral formulation of PL8177 as a possible therapeutic for GI inflammatory diseases in humans.

Evaluation of Intestinal Drug Absorption and Interaction Using Quadruple Single-Pass Intestinal Perfusion Coupled with Mass Spectrometry Imaging.

Visualization and characterization of the intestinal membrane transporter-mediated drug absorption and interaction are challenging due to the complex physical and chemical environment. In this work, an integrated strategy was developed for in situ visualization and assessment of the drug absorption and interaction in rat intestines using quadruple single-pass intestinal perfusion (Q-SPIP) technique coupled with matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). Compared with the traditional SPIP only available for perfusion of one single intestinal segment, the Q-SPIP model can simultaneously perfuse four individual segments of each rat intestine (duodenum, jejunum, ileum, and colon), enabling to obtain rich data from one rat. Subsequently, the drug distribution and absorption in rat intestinal tissue were accurately visualized by using an optimized MALDI MSI approach. The utility and versatility of this strategy were demonstrated via the examination of P-glycoprotein (P-gp)-mediated intestinal absorption of berberine (BBR) and its combination with natural products possessing inhibitory potency against P-gp. The change in the spatial distribution of BBR was resolved, and MALDI results showed that the signal intensity of BBR in defined regions was enhanced following coperfusion with P-gp inhibitors. However, enhanced absorption of BBR after coperfusion with the P-gp inhibitor was not observed in the ulcerative colitis rat model, which may be due to the damage to the intestinal barrier. This study exemplifies the availability and utility of Q-SPIP coupled with MALDI MSI in the examination of transporter-mediated intestinal drug absorption and interaction for fundamental inquiries into the preclinical prediction of oral absorption and drug interaction potential.

Metagenomic analysis of Tongxie Yaofang therapy for rat models of ulcerative colitis with liver depression and spleen deficiency syndrome

Tongxie Yaofang (TXYF) has therapeutic effect on the ulcerative colitis (UC) with liver depression and spleen deficiency syndrome. This study investigated the changes in the gut microbiota of UC rats treated with TXYF. Wistar rats were divided into three groups: Control, dinitrobenzene sulfonic acid (DNBS)-colitis, and DNBS + TXYF (n = 8 per group). UC model was constructed via intrarectally injection of DNBS (25 mg DNBS and 0.25 mL 50% ethanol); rats in DNBS + TXYF group were administered with TXYF (20.8 g/kg) for 21 days. Physiological parameters were measured. Five samples from each group were selected for metagenomic analysis. TXYF treatment significantly reduced disease activity index, colon mucosal damage index, and tumor necrosis factor-alpha level. TXYF treatment prevented DNBS-induced dysregulation of gut microbial communities. Compared with DNBS-colitis group, the abundance of Firmicutes increased significantly and that of Bacteroidetes and Proteobacteria decreased in DNBS + TXYF group. Pathways such as protein processing in the endoplasmic reticulum pathway was enriched in the DNBS-colitis group, whereas it was decreased in the DNBS + TXYF group. Thus, TXYF treatment could effectively restore the dysregulation of intestinal flora induced by UC.

Yiyi Fuzi Baijiang Powder Alleviates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats via Inhibiting the TLR4/NF-κB/NLRP3 Inflammasome Signaling Pathway to Repair the Intestinal Epithelial Barrier, and Modulating Intestinal Microbiota.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease of the intestine, which is prone to recurrence and difficult to cure. Yiyi Fuzi Baijiang powder (YFBP), as a classic Chinese herbal formula, is commonly used in the clinical treatment of UC. However, its potential mechanism remains unclear. In this study, we investigated the mechanism by which YFBP exerts a therapeutic effect against UC. Firstly, we used network pharmacology to screen the active ingredients and potential targets of YFBP and constructed a "drug-ingredient-target" network. Based on bioinformatics, we searched for differentially expressed genes (DEGs) associated with UC and obtained common targets. The core targets of YFBP in the treatment of UC were identified using a protein-protein interaction (PPI) network, and molecular docking techniques were used to evaluate the binding energies of the core targets and corresponding ingredients. Enrichment analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that YFBP exerted therapeutic effects by regulating multiple inflammatory pathways including TLR4, NF-κB, and TNF. Secondly, an experimental study was carried out in vivo for verification. Our results demonstrated that YFBP could effectively improve the symptoms and intestinal pathological of UC rats. Further study showed that YFBP could significantly downregulate the expressions of TLR4 and p-NF-κB p65 in UC rats, inhibit the activation of NLRP3 inflammasome, reduce the levels of IL-1β and TNF-α, and then upregulate the expressions of tight junction proteins in intestinal epithelial cells. In addition, YFBP could improve the intestinal microbial community. In conclusion, our study revealed that YFBP had a good therapeutic effect on UC, and its mechanism might be related to the inhibition of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway to repair intestinal epithelial barrier and the modulation of intestinal microbiota.

Kangfuxin alleviates ulcerative colitis in rats by inhibiting NF-κB p65 activation and regulating T lymphocyte subsets.

Ulcerative colitis (UC) remains an enduring, idiopathic inflammatory bowel disease marked by persistent mucosal inflammation initiating from the rectum and extending in a proximal direction. An ethanol extract of Periplaneta americana L., namely Kangfuxin (KFX), has a significant historical presence in Traditional Chinese Medicine and has been broadly utilized in clinical practice for the treatment of injury. Here, we aimed to determine the effect of KFX on 2,4,6-trinitro'benzene sulfonic acid (TNBS)-induced UC in Sprague-Dawley rats. We established the UC model by TNBS/ethanol method. Then, the rats were subject to KFX (50, 100, 200 mg/kg/day) for 2 weeks by intragastric gavage. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), and histopathological score were evaluated. The colonic tissue interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-1 (TGF-β1), and epidermal growth factor (EGF) were determined by Elisa. To study T-lymphocyte subsets, flow cytometry was performed. In addition, the expression level of NF-κB p65 was evaluated by immunohistochemistry and western blot analysis. Compared with the TNBS-triggered colitis rats, the treatment of rats with KFX significantly increased the body weight, and decreased DAI, CMDI, and histopathological score. Also, KFX elicited a reduction in the secretion of colonic pro-inflammatory cytokines, namely IL-1β, IL-6, and TNF-α, concomitant with up-regulation of IL-10, TGF-β1, and EGF levels. Upon KFX treatment, the CD3+CD4+/CD3+CD8+ ratio in the spleen decreased, while the CD3+CD8+ subset and the CD3+CD4+CD25+/CD3+CD4+ ratio demonstrated an increase. In addition, the expression of NF-κB p65 in the colon was decreased. KFX effectively suppresses TNBS-induced colitis by inhibiting the activation of NF-κB p65 and regulating the ratio of CD4+/CD8+.

Lactobacillus Acidophilus Regulates the Expression of MicroRNAs and Ameliorates the Symptoms of Acid-induced Ulcerative Colitis in Rats

Lactobacillus Acidophilus Regulates the Expression of MicroRNAs and Ameliorates the Symptoms of Acid-induced Ulcerative Colitis in Rats

Apigenin and Exposure to Low Dose Gamma Radiation Ameliorate Acetic Acid-Induced Ulcerative Colitis in Rats.

Ulcerative colitis (UC) is an inflammatory bowel disease involving chronic and recurring colon inflammation. Current management protocols are limited by adverse effects or short-term symptomatic relief. We aimed to investigate the possible therapeutic prospect of low dose gamma (γ) irradiation or apigenin treatment in acetic acid-induced UC in rats. Induction of UC was carried out by installation of acetic acid intra-rectally. One hour post-induction, rats received a sole dose of γ-radiation (0.5Gray) or were treated with apigenin (3mg/kg/day, peroral) for 7 successive days. Antioxidant and anti-inflammatory effects of both agents were assessed via determination of colon malondialdehyde (MDA), reduced glutathione (GSH), total nitrate/nitrite (NOx), mucosal addressin cell adhesion molecule-1 (MAdCAM-1), and interleukin-1beta (IL-1β) contents as well as myeloperoxidase (MPO) activity. Body weight (BW), colon weight/length (W/L) ratio, disease activity index (DAI), and histopathological changes were evaluated. Gamma irradiation and apigenin significantly ameliorated the acetic acid-induced biochemical and histopathological changes. Both therapeutic approaches significantly restored colon contents of the investigated biomarkers. They modulated BW, colon W/L ratio and DAI. This study proposes low dose γ-irradiation as a new therapeutic candidate for the management of UC. We also concluded that apigenin exhibited therapeutic benefits in UC management.

Boswellic acid coated zinc nanoparticles attenuate NF-κB-mediated inflammation in DSS-induced ulcerative colitis in rats.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1β, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1β, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1β, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.

The effect of olsalazine of chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt in BALB/c mice.

To explore effect and mechanism of olsalazine of Chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in BALB/c mice. The mouse model of ulcerative colitis was induced by free drinking of 3% (w/v) DSS aqueous solution for seven days. The mice were treated with olsalazine (0.6 g·kg-1) of Chinese generic drugs. The therapeutic effect of olsalazine on ulcerative colitis mice was evaluated by measuring disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS), and detected the expression levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1β in serum and IL-7, IL-17, IL-22, epidermal growth factor (EGF), transforming growth factor β1 (TGF-β1) in colonic homogenate of mice. Olsalazine significantly increased the contents of IL-2, IL-10, IL-22, TGF and EGF in ulcerative colitis rats, and significantly decreased the scores of DAI, CMDI, HS and the contents in IL-7, IL-17, TNF-α, IL-1β and IFN-γ when compared with the model group. It improved the degree of colonic lesion in ulcerative colitis mice. It was suggested that olsalazine has a therapeutic effect on ulcerative colitis induced by DSS in mice, and the mechanism may be related to the increase of IL-2, IL-10, IL-22, TGF, and EGF and the decrease of the expression of IL-7, IL-17, TNF-α, IL-1β, and IFN-γ.

Mesenchymal Stem Cells Improve Rat Ulcerative Colitis through Activation of the TLR9/MyD88 Pathway

Mesenchymal Stem Cells Improve Rat Ulcerative Colitis through Activation of the TLR9/MyD88 Pathway

Sishen Wan Treats Ulcerative Colitis in Rats by Regulating Gut Microbiota and Restoring the Treg/Th17 Balance.

This study was aimed to explore the mechanism of Sishen Wan (SSW) in treating ulcerative colitis (UC) in a rat model of spleen-kidney yang deficiency pattern by regulating gut microbiota and the content of butyric acid in short-chain fatty acid (SCFAs) and restoring regulatory T (Treg)/T helper type 17 (Th17) balance from the perspective of the correlation between gut microbiota and immune function. The UC rat model of spleen-kidney yang deficiency pattern was established by the method of combining disease and syndrome (intragastric administration of senna leaf, subcutaneous injection of hydrocortisone, and enema with 2,4-dinitrobenzenesulfonic acid (DNBS)/ethanol solution). After successful modeling, rats were randomly divided into six groups: the blank group, model group, low-, middle-, and high-dose Sishen Wan groups, and mesalazine group. Samples were taken after continuous administration for 3 weeks. The general conditions and body weight of the rats were observed and recorded, and the disease activity index (DAI) score was calculated. Colonic mucosal injury was observed, and a colonic mucosal damage index (CMDI) score was calculated. Histopathological changes in colon tissues were determined by hematoxylin and eosin (H&E) staining, and the histopathological score (HS) was calculated. The serum levels of transforming growth factor-β1 (TGF-β1), interleukin (IL)-6, IL-10, and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA) assays. The expression of TGF-β1, signal transducer and activator of transcription 3 (STAT3), and peroxisome proliferator-activated receptor γ (PPARγ) was determined by Western blot analysis. The proportion of Th17 and Treg cells in colon tissue was determined by flow cytometry. The relative abundance of gut microbiota was determined by 16S rDNA sequencing, and the concentration of butyric acid of SCFAs was determined by gas chromatography-mass spectrometry (GC-MS). Administration of SSW significantly improved the pathological changes of colon tissue in UC rats and could attenuate the DAI and CMDI scores, and the HS. SSW significantly decreased the serum levels of IL-6 and IL-17 and increased the serum levels of TGF-β1 and IL-10. In addition, SSW increased the expression of TGF-β1 and PPARγ and decreased the expression of STAT3 in colon tissue in a dose-dependent manner. Furthermore, SSW significantly decreased the proportion of Th17 cells and increased the proportion of Treg cells in colon tissue. Additionally, SSW altered the gut microbiota, including an increase in the relative abundance of Firmicutes and a decrease in Bacteroidota at the phylum level and an increase in the relative abundance of Lactobacillus at the genus level. Moreover, SSW significantly increased the concentration of butyric acid. Combined, these data suggested that SSW increased the relative abundance of firmicutes and the level of butyric acid and restored the balance of Treg/Th17 immune axis and gut homeostasis, thus delaying the progress of UC.

Anti-inflammatory and antioxidant potential of Artemisia dracunculus L. aqueousextract against acetic acid induced ulcerative colitis in male Wistar rats

Ulcerative colitis (UC) is one of the two types of inflammatory bowel disease (IBD) which is increasing worldover due to modern life style. Patients with UC are prone to develop colorectal cancer. While the disease severity decides the treatment option, researchers look towards herbal medicines with anti-inflammatory properties for minimal or nil side effects. Artemisia dracunculus L., commonly called Tarragon, is a medicinal herb used in traditional Asian medicine mainly in Iran, India, Pakistan and Azerbaijan due to its special compounds. In this study, we tried to elucidate the effects of aqueous extract of tarragon on acetic acid induced ulcerative colitis (UC) in rats. Male Wistar rats were grouped into four groups of eight each viz., control; experimental control (UC was induced via luminal instillation of 4% acetic acid); and UC induced + aqueous tarragon extract (100 mg/kg) or prednisolone (2 mg/kg) orally for ten consecutive days. Tissue specimens were collected after the experimental period for evaluation of caspase-3 and cyclooxygenase-2 (COX-2) expression by immunohistochemistry. Real-time PCR was used to monitor the levels of IL-1, IL-6 and TNF-α in colonic homogenates. Moreover, the levels of myeloperoxidase, nitric oxide and total antioxidant capacity were measured in colonic homogenates. The results showed that both treatment regimens could similarly reduce the severity of disease symptoms. Treatment with aqueous extract of tarragon caused a better improvement (P <0.05) in the levels of myeloperoxidase enzyme, and total antioxidant capacity of colonic homogenates compared to prednisolone. Nevertheless, the levels of the expression of caspase-3, and COX-2 and TNF-α were reduced in UC rats received prednisolone more than UC rats received aqueous extract of tarragon. The was no statistical difference in the levels of nitric oxide, IL-1 and IL-6 between UC rats received tarragon extract or prednisolone. Overall, these findings suggest that the aqueous extract of tarragon is a promising strategy to control ulcerative colitis. Aqueous extract can also be used as an anti-inflammatory and immune system stimulant in conditions where the immune system is damaged.

Xianglian pill modulates gut microbial production of succinate and induces regulatory T cells to alleviate ulcerative colitis in rats

Ethnopharmacological relevanceXianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear. Aim of the studyOur previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology. Materials and methodsUC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes. ResultsXLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1α pathway via decreasing microbial succinate production. ConclusionsOur findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis.

Potential mechanisms of Lian-Zhi-Fan solution for TNBS-induced ulcerative colitis in rats via a metabolomics approach.

Lian-Zhi-Fan (LZF) decoction is a hospital-prescribed traditional Chinese medicine botanical drug prepared by the fermentation of decocted Coptidis Rhizome (Huanglian), Gardeniae Fructus (Zhizi), and alum (Baifan). It has been used clinically in China for the treatment of anal fistula, perianal abscess, ulcerative colitis (UC), and other anorectal diseases for hundreds of years. However, due to the complexity of traditional Chinese medicine, the potential mechanisms of LZF in the treatment of UC have remained unknown. This study primarily investigated the remarkable pharmacological effects of LZF on TNBS-induced UC rats. To explore the complex targets and regulatory mechanisms of metabolic networks under LZF intervention, a metabolomics approach mediated by HPLC/Q-TOF-MS analysis was used to screen the different metabolites and their metabolic pathways in the serum in order to characterize the possible anti-UC mechanisms of LZF. After rectal administration of LZF for seven consecutive days, significant amelioration effects on body weight loss, DAI score, and colon inflammation were found in UC rats. Based on this, further metabolomics identified 14 potential biomarkers in the treatment of UC with LZF, of which five possessed diagnostic significance: L-alanine, taurocholic acid, niacinamide, cholic acid, and L-valine. These metabolites are mainly involved in 12 metabolic pathways, including nicotate and nicotinamide metabolism, glycospholipid metabolism, arginine and proline metabolism, primary bile acid biosynthesis, and pantothenate and CoA biosynthesis. These metabolic pathways suggest that LZF ameliorates UC by regulating amino acid metabolism, fat metabolism, and energy production. This study provides a useful approach for exploring the potential mechanisms of herbal prescription in UC treatment mediated by metabolomics.

Molecular and Immunological Studies of Phloretin and Escherichia Coli on Experimentally Induced Ulcerative Colitis in Rats

Molecular and Immunological Studies of Phloretin and Escherichia Coli on Experimentally Induced Ulcerative Colitis in Rats

The Effects of Hyphaena thebaica and Lactobacillus in Dextran Sodium Sulphate-Induced Ulcerative Colitis in Rats

The Effects of Hyphaena thebaica and Lactobacillus in Dextran Sodium Sulphate-Induced Ulcerative Colitis in Rats

Pretreating mesenchymal stem cells with IL-6 regulates the inflammatory response of DSS-induced ulcerative colitis in rats

The immunomodulatory properties of mesenchymal stem cells (MSCs) have been broadly investigated in research on inflammatory diseases including ulcerative colitis. Treating MSCs with an inflammatory stimulus before transplantation is an adaptive strategy that helps MSCs survive in areas of inflammation and promotes the regulation of local immune responses. This study aimed to examine the effects of pretreating bone marrow MSCs (BMSCs) with Interleukin-6 (IL-6) on attenuation of dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. Experimental ulcerative colitis was induced in Wistar rats by administering 2% DSS in their water for 7 days and normal water for the next 3 days. The experimental group received 1 × 106/0.4 ml of BMSCs that were treated with IL-6 for 24 h. Histological changes, colon length, and disease activity index were compared among groups, and the levels of TNF-α, IL-6, and IL-1β in homogenate supernatants were evaluated using ELISA. IL-6-pretreated BMSCs significantly reduced the colonic damage score. The colon length shortened by 6.1 ± 0.14 cm for the rats that received IL-6-pretreated BMSCs, whereas the control group rats' value was 3.8 ± 0.14 cm on the 14th day. The levels of pro-inflammatory cytokines were significantly decreased in the colons of the IL-6-pretreated BMSCs group compared with those of the control group (p < 0.05). This study revealed that IL-6-pretreated BMSCs ameliorated DSS-induced colitis via local anti-inflammatory action and suggested that IL-6-pretreated BMSCs are a promising therapeutic agent for ulcerative colitis treatment.

Targeting endoplasmic reticulum stress, Nrf-2/HO-1, and NF-κB by myristicin and its role in attenuation of ulcerative colitis in rats

AimsUlcerative colitis (UC) is characterized by the up-regulation of pro-inflammatory mediators, apoptotic signals, and oxidative stress that can lead to an increased risk of colorectal cancer. The present study aims to investigate the possible role of myristicin in modulating endoplasmic reticulum stress (ERS) and risk-associated conditions in acetic acid (AA)-induced UC. Materials and methodsAdult male rats were treated with 150 mg/kg body weight of myristicin or mesalazine orally either as pre/post treatment or post-treatment only. The gene expression of glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and nuclear factor kappa B (NF-κB), percentage of DNA fragmentation, and serum levels of some oxidative and inflammatory markers were measured. Key findingsThe results indicated the potential upregulation of ERS, pro-apoptotic, lipid peroxidation, and pro-inflammatory cascades by induction of UC in rats. However, myristicin could effectively reverse the deteriorated effects of ulceration in colonic mucosa. It was mediated through downregulation of the ERS markers GRP78 and CHOP genes expression, reduction of NF-κB mRNA expression, DNA fragmentation, reduced lipid peroxidation, myeloperoxidase (MPO) activity and pro-inflammatory markers (Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β) and cyclo‑oxygenase (COX-2) activity). Accompanied by elevated levels of IL-10, colonic Nuclear erythroid factor (Nrf-2) and Heme oxygenase (HO-1) activity as well as blood antioxidant enzymes activity. Results of docking might confirm the biological results of our study. SignificanceMyristicin could effectively modulate important stress, and inflammatory effectors and protect mucosal DNA from oxidative damage which can serve as a promising candidate for the treatment of ulcerative colitis.

Network pharmacology and in vivo experiment-based strategy to investigate mechanisms of JingFangFuZiLiZhong formula for ulcerative colitis

Background Ulcerative colitis (UC), a chronic inflammatory disease, often cause carcinogenesis, disability, and intestinal perforation. The JingFangFuZiLiZhong formula (JFFZLZ) shows a good effect against UC in the clinic. Hence, we aim to investigate the mechanisms between JFFZLZ and UC via network pharmacology data mining and in vivo experiments. Methods We obtained active constituents and related targets from public databases. The overlapped genes between JFFZLZ and UC targets were further analysed by enrichment analysis. The active constituents and hub targets were used to construct molecule docking analysis. We finally screened out nine hub targets and their expressions were verified in the Gene Expression Omnibus database and UC rats’ colon tissues after JFFZLZ treatment. Results The results implied that JFFZLZ mainly regulated signal transduction, metabolites production, and inflammation pathways. The expression of STAT3, CXCL8, IL6, CXCL12, TNF, TP53, and PTPN11 were both upregulated in colon tissues of UC patients and UC rats. While RELA, EGFR, and TP53 were downregulated in UC patients, but upregulated in UC rats. Furthermore, JFFZLZ could repair UC rats’ colon mucosal damage and promote the healing of ulcers via regulating the hub targets. Conclusion These results elucidated that the anti-UC effect of JFFZLZ was closely related to the inhibition of inflammatory response, inhibition of oxidative stress, and repairing colon mucosal damage through different signal pathways. The findings could contribute to a better understanding of the regulation mechanisms in JFFZLZ against UC. Key messages JFFZLZ could reduce the inflammatory infiltration and repair UC rats’ colon mucosal damage. Through the network pharmacology-based strategy and public database mining, we obtained the hub targets and key pathways between JFFZLF and UC. The mechanism of JFFZLZ against UC was inhibition of inflammatory response and oxidative stress by regulating the expression of the hub targets.