Colon Mucosa Damage Index Research Articles

Effect mechanism investigation of herb-partitioned moxibustion on relieving colon inflammation in Crohn disease rats based on neutrophil extracellular traps

ObjectiveTo explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps (NETs) in Crohn disease (CD) development.MethodsRats were randomly divided into a normal group, a model group, a herb-partitioned moxibustion group, and a mesalazine group. The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group. Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups. Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai (CV6) and bilateral Tianshu (ST25). Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets. The general situation of rats in each group was recorded, and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining. The serum concentrations of NETs DNA (NETs-DNA), neutrophil elastase (NE)-DNA, and myeloperoxidase (MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay, and the citrullinated histone 3 (citH3), MPO, and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction.ResultsCompared with the normal group, the mucosal ulcer reached the muscularis, the epithelium was incomplete, the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon; the colonic mucosa damage index (CMDI) score increased significantly (P<0.01); the serum NETs-DNA, NE-DNA, and MPO-DNA concentrations increased (P<0.05); the NE, citH3, and MPO protein and mRNA expression in the colonic tissues increased significantly in the model group (P<0.01 or P<0.05). Compared with the model group, the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon; the CMDI score decreased (P<0.01); the serum NETs-DNA, NE-DNA, and MPO-DNA concentrations decreased (P<0.05); the NE, citH3, and MPO protein and mRNA expression in the colonic tissues was down-regulated (P<0.01 or P<0.05).ConclusionHerb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue, which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Shaoyao decoction alleviates TNBS-induced ulcerative colitis by decreasing inflammation and balancing the homeostasis of Th17/Treg cells

BackgroundUlcerative colitis (UC) is a persistent and non-specific inflammatory condition that mainly affects the bowels and has challenging treatment. UC has a growing incidence and significantly affects the well-being of patients. Many medications used to treat UC can disrupt the metabolism and immune system homeostasis, frequently leading to significant adverse effects. Hence, exploring alternative therapies, such as traditional Chinese medicine and probiotics, has recently emerged as a primary research hotspot owing to their safety. Although the therapeutic mechanism of Shaoyao decoction has not been clarified, it has demonstrated a beneficial clinical effect on UC.AimThis study aimed to assess the effect of Shaoyao decoction on a rat model of UC and investigate its underlying mechanisms.MethodsThe rat model of UC was induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The extent of damage to the intestines was assessed using the disease activity index (DAI), colonic mucosa damage index (CMDI), and histological scores. Immunohistochemistry was employed to detect the tissue levels of interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-10. Additionally, the proportion of Th17 and Treg cells was detected using flow cytometry. In colon tissue, the levels of forkhead box (Fox)p3, RAR-related orphan receptor (ROR)γt, IL-6, p-STAT3, and STAT3 proteins were quantified by Western blotting.ResultsTreatment with Shaoyao decoction enhanced the overall health of rats and reduced colonic damage. Additionally, Shaoyao decoction significantly alleviated the severity of DAI, CMDI, and HS. The proportion of Th17 cells was reduced, and the proportion of Treg cells was increased by Shaoyao decoction. The expression of IL-17 and RORγt was suppressed by Shaoyao decoction, while the expression of IL-10, TGF-β1, and Foxp3 was increased. The expression of IL-6, p-STAT3, and STAT3 was decreased by Shaoyao decoction.ConclusionThe Shaoyao decoction alleviates the symptoms of TNBS-induced UC by decreasing inflammation and mitigating intestinal damage while preserving the balance between Th17 and Treg. Shaoyao decoction modulates the IL-6/STAT3 axis, thereby regulating the balance between Th17 and Treg cells.

Study on the mechanism of Gao-Liang-Huo decoction against dextran sulfate sodium-induced ulcerative colitis based on metabolomics and network pharmacology

BackgroundsGao-Liang-Huo decoction (GLH), a traditional Chinese medicine consisting of gao liangjiang (the roots or tubers of Alpinia offinarum Hance) and guang huoxiang (the aerial parts of Pogostemon cablin (Blanco) Benth.), has been shown an effective therapeutic efficacy for ulcerative colitis (UC). However, the active compounds and underlying mechanisms involved in GLH treatment of UC remains unclear. This study aims to investigate the pharmacological mechanism of GLH on UC using an integrated strategy of metabolomics and network pharmacology. MethodsThe experimental mice UC model was induced using dextran sulfate sodium (DSS). The disease activity index (DAI), colonic mucosa damage index (CMDI), biochemical assays, and histopathological analysis were used to evaluate the pharmacological effect of GLH. The LC/MS-based metabolomics was used for investigation of serum metabolites and metabolic pathways regulated by GLH. The potential targets and pathways of the active compounds in GLH were further explored using network pharmacology. Finally, the underlying mechanism of GLH on UC was verified by molecular docking and immunohistochemistry (IHC). ResultsThe pharmacological experiments showed that GLH significantly ameliorated the DAI, CMDI, MDA, MPO, and histopathological changes in DSS-induced UC. The 15 metabolites were identified by metabolomics, such as L-tryptophan, taurocholic acid, glycocholic acid, 3-indolebutyric acid, and tryptophol. These metabolites were found to be enriched in tryptophan metabolism, glycerophospholipid metabolism, and citrate cycle (TCA cycle). The results of network pharmacology revealed the key targets, such as PIK3CA, PIK3R1, JAK1, JAK2, and JAK3, mainly involved in the PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. Molecular docking showed high affinity interaction of quercetin, isorhamnrtin, poriferast-5-en-3beta-ol, 1,7-diphenyl-5-hydroxy-3-heptanone, and medicarpin with PIK3CA, PIK3R1, JAK1, JAK2, and JAK3, respectively. Finally, the immunohistochemistry (IHC) results indicated that GLH regulated the PI3K-AKT pathway with decreased expression levels of PI3KCA and p-AKT in DSS-induced UC. Based on integration of pharmacological experiments, network pharmacology, and metabolomics suggested that GLH might improve DSS-induced US by modulating tryptophan metabolism, glycerophospholipid metabolism, PI3K-AKT, JAK-STAT, and T-cell receptor signaling pathways. ConclusionsThis study highlights the potential of combining metabolomics and network pharmacology as a promising strategy for exploring the potential mechanism of TCMs.

Acalypha australis L. Extract Attenuates DSS-Induced Ulcerative Colitis in Mice by Regulating Inflammatory Factor Release and Blocking NF-κB Activation.

Ulcerative colitis (UC) is a chronic gastroenteric inflammatory disease that may cause life-threatening complications. Currently available therapeutic drugs are not as effective as expected, necessitating the development of new targets and drugs. The etiology and pathogenetic mechanisms of UC are largely unclear; thus, the treatment effects are limited. The aqueous extract of Acalypha australis L. (AAL) has shown good therapeutic efficacy in treating UC. AAL is used in traditional Chinese medicine owing to its hemostasis, detoxification, and heat clearance effects. Although astragalus has such broad-spectrum biological activities closely related to inflammation, its therapeutic efficacy for UC treatment has not been reported, the underlying mechanism remains unknown. We studied the therapeutic effect of AAL on UC in mice and explored its potential mechanism. Mice were treated with AAL aqueous extract for 7 days (20 mg/kg), after which the colon tissue was assessed for damage (colon mucosal damage index [CMDI]), apoptosis (immunohistochemistry), and release of cytokines (enzyme-linked immunosorbent assay). The concentration of AAL aqueous extract at 20 mg/kg significantly improved the CMDI score and colon injury of UC model. It also reduced the serum levels of IL-2, IL-8, IL-17A, IL-22, IFN-γ, and TNF-α, and decreased apoptosis in the colon. AAL water extract also significantly reduced the expression level of NF-κB pathway-related proteins. In conclusion, AAL can protect against UC mainly by inhibiting the expression level of NF-κB pathway-related proteins and reducing the release of inflammatory factors.

Oral intake of titanium dioxide nanoparticles affect the course and prognosis of ulcerative colitis in mice: involvement of the ROS-TXNIP-NLRP3 inflammasome pathway

BackgroundTitanium dioxide (TiO2), no matter in nanoscale or micron sizes, has been widely used in food industry as additives for decades. Given the potential impact of TiO2 on the gastrointestinal epithelial and parenchymal cells, including goblet cells, the public consumers may suffer the risk of diseases caused by its widespread dissemination in food products. We therefore set out to investigate the impact of TiO2 NPs on the course and prognosis of ulcerative colitis by oral gavaging TiO2 NPs at the doses levels of 0, 30, 100, and 300 mg/kg during the induction (7 days, from day 1 to day 7) and recovery (10 days, from day 8 to day 17) phases of colitis in mice.ResultsThe ulcerative colitis (UC) disease model was established by administrating of 2.5% dextran sulfate sodium (DSS) solution. Our results show that TiO2 NPs significantly enhanced the severity of DSS-induced colitis, decreased the body weight, increased the disease activity index (DAI) and colonic mucosa damage index (CMDI) scores, shortened the colonic length, increased the inflammatory infiltration in the colon. The most significant changes occurred in the low dose (30 mg/kg) group of TiO2 NPs exposure during the development phase of UC and the high dose (300 mg/kg) group of TiO2 NPs during UC self-healing phase. Increased reactive oxygen species (ROS) level and upregulation of anti-oxidant enzymes including total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-PX) and catalase (CAT), demonstrate that the TiO2 NP exposure has triggered oxidative stress in mice. Moreover, the upregulation of caspase-1 mRNA and increased expression of thioredoxin interacting protein (TXNIP) further demonstrate the involvement of the ROS-TXNIP-NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in aggravating the development of UC.ConclusionOral intake of TiO2 NPs could affect the course of acute colitis in exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.Graphical

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.

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.

Berberine promotes M2 macrophage polarisation through the IL-4-STAT6 signalling pathway in ulcerative colitis treatment

AimThis study focusses on the anti-inflammatory and immune-modulatory roles of berberine (BBR) in ulcerative colitis (UC) treatment. Additionally, the underlying mechanisms of BBR were systematically explored. MethodsA 3% (w/v) dextran sodium sulphate (DSS) solution was used for establishing the mice UC model. M2 macrophage polarisation was induced in RAW 264.7 cells using interleukin 4 (IL-4), whereas M1 macrophage polarisation was induced using lipopolysaccharide. Colon length, colon mucosa damage index (CMDI), and haematoxylin–eosin (HE) staining were used to evaluate colon damage induced by DSS. M1/M2 macrophages in the colon tissue were identified using immunofluorescence (IF) staining with CD86+ or CD163+. M1/M2 macrophages in the abdomen were examined using flow cytometry. An enzyme-linked immunosorbent assay was conducted to identify M1/M2 macrophage supernatant biomarkers in RAW 264.7 cells. Western blotting, immunohistochemical staining, and real-time PCR were performed to investigate the potential mechanisms of BBR for treating UC in vivo and in vitro. ResultsBBR was found to prolong colon length, ameliorate CMDI and alleviate the colon's pathological changes in UC mice. In DSS-induced UC mice, M1 macrophages predominated. BBR promoted M2 macrophages and suppressed M1 macrophages in the colon and abdomen of DSS-induced UC mice. Additionally, BBR significantly decreased M1-specific markers (IFN-γ and IL-1β) while increasing M2-specific markers (IL-10 and TGF-β) in the supernatants of RAW 264.7 cells. BBR upregulated the mRNA expression of IL-4, STAT6, and Chil3 while downregulating TNF-α, IFN-γ, and NOS2 expression in vivo. Moreover, BBR activated the downstream targets of the IL-4-STAT6 signalling pathway and enhanced the phosphorylation of STAT6 in vivo and in vitro to polarise M2 macrophage. ConclusionIn UC mice, BBR suppressed M1 macrophages while promoting M2 macrophages. M1 macrophage suppression and M2 macrophage activation were strongly correlated with the anti-inflammatory and immune-modulating activities of BBR. BBR induced the polarisation of M2 macrophages by activating the IL-4-STAT6 signalling pathway, which contributed to its therapeutic efficacy against UC.

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.

The beneficial effects of Fomitopsis pinicola chloroform extract on a dextran sulfate sodium-induced ulcerative colitis mice model.

As an intestinal non-specific inflammatory lesion, ulcerative colitis (UC) affects the health of many individuals. This study examined the possible beneficial effects of the chloroform extract of Fomitopsis pinicola (Swartz.: Fr) Karst (FPKc) on UC. The mice were given free access to drink with 4% dextran sulfate sodium (DSS) for 1 week to establish acute UC model. Next, 35 mg of FPKc or sulfasalazine (SASP) was given to the mice via gavage for 3 weeks. The disease activity index (DAI) and colonic mucosa damage index (CMDI) scores were calculated. The colon tissues of the mice were collected to measure the length and perform hematoxylin and eosin staining. The thymus and spleen indexes were determined. Interleukin (IL)-6, IL-8, tumor necrosis factor-α, aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were determined. FPKc or SASP treatment alleviated hematochezia and weight loss, ameliorated DAI and CMDI scores, and improved the crypt structure and length of the colon tissues. Relative to the UC model group, the spleen index in the FPKc group was reduced, which was accompanied by decreases of the IL-6 and IL-8 levels in the serum. FPKc also lowered the AST and ALT levels in the serum of the UC mice. FPKc protected the mice from DSS-induced UC injury. It may be that FPKc activates immune regulation and downregulates the expression of pro-inflammatory cytokines.

Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis.

The rectal enemas of berberine hydrochloride (BH) have emerged as one of the most effective strategies in the clinical treatment of ulcerative colitis (UC). However, oral dosages of BH exhibit a poor anti-inflammatory effect of UC, which may attribute to premature absorption of BH by the upper gastrointestinal tract. Moreover, the thick colonic mucus layer obstructs the penetration of the drug, resulting in low bioavailability to the inflammatory site of the colon. The aim of this study was to develop the mucus-penetrating sodium alginate-chitosan nanoparticles (SA-CS NPs) for oral delivery of BH to the site of colonic ulcer lesions. BH-loaded SA-CS NPs were developed through the ionic gelation method and analyzed for physicochemical characteristics, release performance, penetrability, site retention, and therapeutic efficacy. The results showed that the NPs have a particle size of 257 nm with a negative charge, presenting desired pH-dependent release behavior. The permeation studies elucidated that negatively charged SA-CS NPs had 2.9 times higher mucus penetration ability than positively charged CS NPs. An ex vivo retention study indicated the high retention of BH-SA-CS NPs at the colon site for more than 16 h. In vivo therapeutic effectiveness demonstrated that the prepared NPs could not only alleviate colonic injury by decreasing the disease activity index and colon mucosa damage index, but also improve the immunologic function by decreasing the spleen index. In conclusion, the BH-SA-CS NPs could enhance the mucus permeability and deliver drugs to the colonic inflammation site, providing new insights into improving the therapeutic effect of UC.

Electroacupuncture of "Shangjuxu"(ST37) and "Tianshu"(ST25) reduces colonic injury by suppressing NF-κB/NLRP3 signaling in rats with ulcerative colitis

To observe the effect of electroacupuncture (EA) of "Shangjuxu"(ST37) and "Tianshu"(ST25) on colonic mucosal injury and activities of nuclear factor-κB (NF-κB)/Nod-like receptor family，pyrin domain-containing 3 (NLRP3) inflammasome signaling in the colonic tissue in rats with ulcerative colitis (UC), so as to explore its mechanisms underlying improvement of UC. Male SD rats were randomly divided into blank, model, medication and EA groups, with 12 rats in each group. The UC model was established by enema of 2-4-6 trinitrobenzene sulfonic acid +50% ethanol (2.5 mL). EA (10 Hz/50 Hz) was applied to bilateral ST37 and ST25 for 20 min, once a day, for a total of 10 days. Rats of the medication group received gavage of mesalazine suspension (2 mL：0.2 g/kg+0.9% saline) once a day, for 10 days. The rats' general conditions were recorded for calculating the disease activity index (DAI) score (0-4 points). The colonic tissue was sampled for giving colonic mucosa damage index (CMDI, 0-5 points) score and for observing histopathological changes after hematoxylin-eosin (HE) staining, and for detecting expression levels of NF-κB and NLRP3 by using immunohistochemistry and Western blot, separately. The contents of serum interleukin-1β (IL-1β), NLRP3 and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with the blank group, the DAI and CMDI scores, contents of serum IL-1β, NLRP3, and TNF-α, as well as the immunoactivity and expression of NF-κB and NLRP3 proteins were significantly increased in the model group (P<0.05). Relevant to the model group, modeling-induced increases of DAI and CMDI scores, serum IL-1β, NLRP3 and TNF-α contents, and NF-κB and NLRP3 expression were reversed in both medication and EA groups (P<0.05), the effect of EA was apparently superior to that of mesalazine in down-regulating CMDI score and serum IL-1β level (P<0.05). No significant diffe-rences were found between the medication and EA groups in down-regulating DAI score, serum TNF-α and NLRP3 contents, and expression of NF-κB and NLRP3 proteins (P>0.05). The rats' general conditions including arch back sloth, anorexia, loss of fur gloss, weight loss, lethargy and loose of stool, and histopathological changes such as necrosis of intestinal mucosa, formation of obvious ulcerative surface, with many neutrophils and pus cells and inflammatory cell infiltration were obvious in the model group, which were relative milder in both medication and EA groups. EA can relieve colonic injury in UC rats, which may be related to its functions in down-regulating serum IL-1β, TNF-α and NLRP3 levels by suppressing colonic NF-κB / NLRP3 inflammasome signaling.

Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling.

Protective Effect of Nelumbo nucifera Plant on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Rats

Objectives Ulcerative colitis is a global disease with increasing incidence and worldwide prevalence. So this study was undertaken to observe antiulcerative colitis activity of ethanolic extract of seeds of Nelumbo nucifera plant on dextran sodium sulfate (DSS)-induced ulcerative colitis in rats. Materials and Methods The effect of ethanolic extract of N. nucifera seed (EENNS) was studied on DSS-induced ulcerative colitis in albino Wistar rats for 11 days. Disease pathogenesis was assessed by evaluation of disease activity index (DAI) including the following parameters: change in body weight, stool constituency, rectal bleeding in animals. Estimation of myeloperoxide (MPO), nitric oxide (NO), and antioxidant parameters like malondialdehyde (MDA), superoxide dismutase (SOD), and catalase level was performed in colon homogenate of animals. TNF-α (tumor necrosis factor- α) level was measured in colon homogenate using rat TNF-α ELISA kit. Statistical Analysis Significant differences (mean ± standard error of the mean) were detected using one-way analysis of variance followed by post-test using Graphpad prism 7.0 for multiple comparisons. Results EENNS (400 mg/kg) significantly improved the disease progression, body weight, and colon length of the animals as compared with the disease control group. Animal treated with EENNS (400 mg/kg) showed significantly improved colon mucosal damage index (1.66 ± 0.21) and DAI (11.66 ± 4.01) as compared with the disease control group. A higher level of SOD and catalase and a lower level of MDA were observed in animals treated with EENNS (400 mg/kg) as compared with the disease control group. Animals treated with EENNS (400 mg/kg) significantly decreased in NO and MPO levels as compared with the disease control group. A lower level of TNF-α (561.94 ± 14.84) was observed in EENNS (400 mg/kg)-treated animals as compared with the disease control group (736.92 ± 15.3). These observations were comparable to those of the standard control group. Histopathological data showed that EENNS (400 mg/kg) has shown reversal of tissue inflammation as compared with the disease group and evidence of less cell infiltration of lymphocytes and monocytes with normal structures of goblet cell and crypts as compared with the disease group. Conclusion EENS (400 mg/kg) can decrease the severity of the UC produced by DSS. EENNS showed a protective effect against DSS-induced ulcerative colitis which may be due to its antioxidant and anti-inflammatory activity.

Effects of the Traditional Chinese Medicine Formula Ento-PB in Experimental Models of Ulcerative Colitis

The traditional Chinese medicine (TCM) formula Ento-PB containing Periplaneta americana (Linnaeus) (Blattidae) and Taraxacum mongolicum Hand.-Mazz. (Compositae) has great potential for treating inflammation. This study explored the effects of Ento-PB on ulcerative colitis (UC). The UC model was induced with 2,4,6-trinitrobenzene sulfonic acid (TNBS) by enema. Male Sprague–Dawley rats (n = 32) were divided into four groups: (1) control group that received 2.5 mL/kg normal saline, (2) TNBS group that received 2.5 mL/kg normal saline, (3) Ento-PB low-dose group that received 100 mg/kg Ento-PB, and (4) Ento-PB high-dose group that received 200 mg/kg Ento-PB. Rats were administered drugs via enema for 14 days after modeling. The disease activity index (DAI), colon mucosa damage index (CMDI), histopathological score (HS), levels of interleukin-8 (IL-8), IL-10, IL-17, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) in serum, contents of IL-2, myeloperoxidase (MPO), transforming growth factor-β1 (TGF-β1), and epidermal growth factor (EGF) in the colon, and abundance of Bifidobacterium, Lactobacillus, Enterococcus, Bacteroides, and Escherichia coli were assessed. Ento-PB administration showed a significant reduction in DAI, CMDI, and HS, contents of IL-2, IL-8, IL-17, TNF-α, CRP, and MPO, and a significant increase in the levels of IL-10, TGF-β1, and EGF. Compared with the TNBS-administered group, the abundance of Bifidobacterium, Lactobacillus, Enterococcus, and E. coli decreased, while an obvious increase in the proportion of Bacteroides was found in the Ento-PB-administered groups. Ento-PB alleviated inflammation in UC by regulating the equilibrium of Th1/Th17/Treg cytokines and recovering the imbalance between the gut microbiota. Applying Ento-PB in treating UC could be suggested.

Dandelion root extracts abolish MAPK pathways to ameliorate experimental mouse ulcerative colitis.

Dextran sodium sulfate (DSS)-triggered ulcerative colitis (UC) model in animals provides a valuable platform to preclinically evaluate the outcome of drug candidates for UC. Dandelion root extracts (DRE) have a therapeutic effect on UC. However, the protective mechanism of DRE against UC remains unknown. To discover the targeting pathway involved in DRE-induced protection against UC. The UC model was developed in C57BL/6 mice by oral administration of DSS. Following DSS exposure, sulfasalazine (SASP), low dose of DRE (DRE-L), moderate dose of DRE (DRE-M), high dose of DRE (DRE-H), and DRE-H plus mitogen-activated protein kinases (MAPK) agonist (DRE-H+MA) were administered to the mice. Colon Mucosal Damage Index (CMDI) and histopathological analysis were used to evaluate the colonic mucosal damage. The cytokine levels were detected using commercial enzyme-linked immunosorbent assay (ELISA) kits. The MAPK pathway activation was determined with western blotting. We found that DRE-H attenuated DSS-triggered colonic mucosal damage. The DSS-induced inflammatory responses and oxidative stress in the bloodstream and colon tissues were dramatically inhibited by DRE-H administration. Also, this plant impaired DSS-provoked phosphorylation levels of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), p65, and IκB. More importantly, MAPK agonist, BIM-23A760, removed the protective effect of DRE-H on the bloodstream and colon tissues. The DRE-H is capable of relieving DSS-induced UC, and its mechanism links to the MAPK pathways.

Pre-Clinical Safety and Efficacy Evaluation of a Herbal Nanoemulsion-Based Formulation for Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic autoimmune sickness that affects the gastrointestinal tract (GIT). Currently available treatment regimens have various adverse effects and create a financial burden. This paper presents the development of an oral liquid formulation containing a nanoemulsion (NE) of herbal extracts for the treatment of IBD. A NE-based formulation was prepared and characterized. Stability studies based on the physical appearance, viscosity, pH, total microbial count, and assay were performed. The antioxidant activity of the individual extract, mixture, and formulation was compared by the DPPH method. In order to assess both the efficacy and the safety of the formulation, a TNBS-induced colitis model was used. A herbal extract of fennel, anise, chamomile, linseed, and pomegranate fruit peel was used as the oil phase, PEG as a surfactant, Tween 80 as a co-surfactant, and benzalkonium chloride (0.001% w/v) as a preservative in the NE. Average particle size, PDI, viscosity, and pH were 283 nm, 0.33, 48 cp, and 5.9, respectively. Assay of the product by standard marker anethole was 99.6%. It was established that the formulation remains stable at least for 6 months. The antioxidant activity of the combined extract was higher than the individual extracts. The colon mucosa damage index (CMDI) from the formulation was negligible and similar to that of the control group. The results suggest that it is worthwhile developing the NE of herbal extracts for treating IBD. Additionally, the benefit of selecting a multi-herb extract for NE formulation is demonstrated by the antioxidant activity of the combined extracts. This study revealed that the NE of the herbal extract is a promising approach for IBD treatment. A patent related to the work is published in the Indian Official Journal of the Patent Office (14/2021).

Mechanism of Sanhuang Decoction in alleviating dextran sulfate sodium induced ulcerative colitis in mice with Candida albicans colonization:based on high-throughput transcriptome sequencing

This study explored the mechanism of Sanhuang Decoction(SHD) in treating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice with Candida albicans(Ca) colonization via high-throughput transcriptome sequencing. Specifically, the animal model was established by oral administration of 3.0% DSS for 7 days followed by intragastrical administration of Ca suspension at 1.0 × 10~8 cells for 4 days and then the mice were treated with SHD enema for 7 days. Afterwards, the general signs were observed and the disease activity index(DAI) was recorded every day. After mice were sacrificed, colon length and colon mucosa damage index(CMDI) were determined and the histomorphology was observed with the HE staining method. The fungal loads of feces were detected with the plate method. Anti-saccharomyces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, and IL-6 in serum and colon were detected by ELISA. High-throughput RNA sequencing method was adopted to identify transcriptome of colon tissues from the control, model and SHD(15.0 g·kg~(-1)) groups. Differentially expressed genes(DEGs) among groups were screened and the GO and KEGG pathway enrichment analysis of the DEGs was performed. The expression levels of NLRP3, ASC, caspase-1, and IL-1β genes related to the NOD-like receptor signaling pathway which involved 9 DEGs, were examined by qRT-PCR and Western blot. The results demonstrated that SHD improved the general signs, decreased DAI and Ca loads of feaces, alleviated colon edema, erosion, and shortening, and lowered the content of β-1,3-glucan in serum and TNF-α, IL-1β, and IL-6 in serum and colon tissues of mice. Transcriptome sequencing revealed 383 DEGs between SHD and model groups, which were mainly involved in the biological processes of immune system, response to bacterium, and innate immune response. They were mainly enriched in the NOD-like signaling pathway, cytokine-cytokine interaction pathway, and retinol metabolism pathway. Moreover, SHD down-regulated the mRNA and protein levels of NLRP3, caspase-1, and IL-1β. In a word, SHD ameliorates DSS-induced UC in mice colonized with Ca, which probably relates to its regulation of NOD-like receptor signaling pathway.

Dendrobium huoshanense Polysaccharides Prevent Inflammatory Response of Ulcerative Colitis Rat through Inhibiting the NF-κB Signaling Pathway.

The polysaccharides of the Chinese herbal medicine Dendrobium huoshanense exhibit anti-inflammatory effects in multiple organs through regulating the immune responses. In the present study, we constructed ulcerative colitis (UC) model rats using dextran sulfate sodium to investigate the anti-inflammatory effects of D. huoshanense polysaccharides (DHP). After oral administration of DHP for two weeks, the indices of UC symptoms, including the ratio of colon weight to length, Disease Activity Index (DAI), and Colon Mucosal Damage Index (CMDI), all decreased significantly compared with the UC model group. The histological sections also revealed better cell orders in DHP treatments than in the UC model rats. Moreover, in treatment with high dose of DHP (200 mg/kg), the treatment efficacy arrived the similar levels to those in the treatment with 300 mg/kg sulfasalazine, which is a typical medicine to treat UC. These results indicated that DHP has a high efficacy to treat UC in model rats. Furthermore, serum levels of interleukin-1β, tumor necrosis factor-α, interleukin-17, and transforming growth factor-β were assessed using the enzyme linked immunosorbent assay (ELISA) method, and the levels of nuclear factor-κB in colon tissue sections were determined using the immunohistochemical method. The results showed that all these indices decreased significantly after administration of DHP in UC model rats, which might be the mechanisms underlying the DHP-suppressed UC inflammation. Overall, this study indicated that DHP might be directly used to treat UC and is a promising source to develop novel drugs against UC.

Kangfuxin Liquid Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Ulcerative Colitis in Mice by Modulating Immune Response and Suppressing Inflammation

BackgroundThe aim of this study was to determine the effect of kangfuxin liquid (KFXL) on inflammatory response, and its underlying mechanism in treating acute ulcerative colitis (UC) in mice induced by dextran sulfate sodium (DSS).Material/MethodsMice were provided drinking water containing DSS (3%) for 7 days to induce acute enteritis. The mice were divided into 6 groups: a control group, a DSS-induced (vehicle) group, a sulfasalazine (SASP) group, and low-, medium-, and high-dose kangfuxin liquid groups. Disease activity index (DAI), colon mucosa damage index (CMDI), histopathological score (HS), and organ index were monitored daily. The levels of interleukin-1β (IL-1β), interleukin-10 (IL-10) in serum and interleukin-17 (IL-17) and epidermal growth factor (EGF) in colon tissue were assessed by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the changes of T lymphocyte subsets in spleens of mice to evaluate the therapeutic effect of drugs on acute UC in mice.ResultsDifferent doses of kangfuxin liquid reduced the DAI, CMDI, and HS scores (P<0.01 or P<0.05) of acute UC mice, reduced the level of IL-1β and IL-17 in serum, increased the expression of IL-10 in serum and EGF in colon tissue, increased the number of CD3+ T cells, and decreased the level of CD4+ T cells and the ratio of CD4+/CD8+.ConclusionsKangfuxin liquid has a therapeutic effect on DSS-induced acute UC in mice, and its mechanism of action may be associated with regulating immune function and reducing intestinal inflammatory response.