DSS-induced Acute Ulcerative Colitis Research Articles

Synergistic effects of probiotics with soy protein alleviate ulcerative colitis by repairing the intestinal barrier and regulating intestinal flora

In this experiment, we used probiotic and soy protein as raw materials to intervene in DSS-induced acute ulcerative colitis in C57BL/6 mice, to investigate the mitigating effect and synergistic effect of the probiotic complex combined with soy protein. The results showed that the combination of probiotics and soy protein could effectively alleviate the symptoms in UC mice, and inhibit the inflammatory process by down-regulating the expression of IL-6 and TNF-α and reducing the infiltration of inflammatory cells. Histopathological results showed that probiotic and/or soy protein interventions were effective in reducing the DAI of colonic ulceration, repairing intestinal epithelial barrier damage, and up-regulating the expression of tight junction-associated proteins. The composition of intestinal microbiota in the SP group, YWSP group and SNSP group with soybean protein intervention showed similar characteristics. In conclusion, the combination of YW probiotic powder and soy protein exerted a good synergistic effect.

Analysis of metagenome and metabolome disclosed the mechanisms of Dendrobium officinale polysaccharide on DSS-induced ulcerative colitis-affected mice

Currently, there is no known cause for ulcerative colitis (UC), an inflammatory bowel disease that is difficult to treat. This assay aimed to investigate the protective effects and mechanisms of Dendrobium officinale polysaccharide (DOP) in mice with acute UC induced by dextran sulphate sodium (DSS). We found that DOP could improve weight loss, decrease the disease activity index (DAI), and regulate the release of interleukin 2 (IL-2), IL-4, IL-6, and IL-10 in DSS-induced acute UC mice. Additionally, DOP preserved the integrity of the intestinal barrier in UC mice by increasing goblet cell density and maintaining tight junctions. DOP significantly enhanced total antioxidant capacity (T-AOC), and reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels in the bloodstream. In terms of serum biochemistry, DOP markedly elevated levels of bilirubin (BIL), alkaline phosphatase (ALP), total bile acid (TBA), creatinine (Crea), and creative kinase isoenzyme (CKMB). Furthermore, DOP increased the relative abundance of Lactobacillales. DOP also improved intestinal health and stimulated the synthesis of potent anti-inflammatory and antiviral substances by regulating the metabolism of purines, prostaglandins, and leukotrienes. Therefore, DOP can be considered a functional dietary supplement for the treatment of UC, as it improves the condition of DSS-induced UC mice.

Gas chromatography-mass spectrometry-based metabolomics reveals the potential mechanism of action of saikosaponin D against DSS-induced acute ulcerative colitis

Gas chromatography-mass spectrometry-based metabolomics reveals the potential mechanism of action of saikosaponin D against DSS-induced acute ulcerative colitis

Explore the underlying oral efficacy of α-, β-, γ-Cyclodextrin against the ulcerative colitis using in vitro and in vivo studies assisted by network pharmacology

The incidence of ulcerative colitis (UC) is rising worldwide. As a refractory and recurrent disease, UC could seriously affect the patients’ quality of life. However, current clinical medical treatments for UC are accompanied by various side effects, especially for long-term applications. Here, the underlying efficacy of cyclodextrins (CDs) was studied. As common excipients, CDs endow proven safety for long-term applications. Results of predictive methods derived from network pharmacology prompted the potential anti-inflammatory effects of CDs by oral administration. RAW264.7 cell experiments verified that CDs could inhibit the excessive secretion of TNF-α (β-CD > α-CD ≈ γ-CD), IL-6, and NO (α-CD > β-CD ≈ γ-CD) as predicted. In mice with DSS-induced acute UC, oral administration of CDs could effectively mitigate the pathological damage of colon tissue and reduce the level of inflammatory mediators. Moreover, 16S rRNA sequencing displayed that gut microbes disturbed by DSS were significantly regulated by CDs. Conclusively, the study showed the therapeutic application prospects of CDs in UC treatment and indicated the feasibility and advantages of developing ‘new’ therapeutic activities of ‘old’ ingredients. Communicated by Ramaswamy H. Sarma

23-Hydroxybetulinic Acid, A Natural Compound, Alleviates DSS-induced Colitis by Regulating NF-κB Signaling

Article 23-Hydroxybetulinic Acid, A Natural Compound, Alleviates DSS-induced Colitis by Regulating NF-κB Signaling Shuangli Xiang 1, # , Miaojuan Wang 2, # , and Xiuping Chen 2, * 1 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou Province, China. 2 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China. * Correspondence: xpchen@um.edu.mo, Tel.: +853-88224679, Fax: +853-28841358 # Co-First author. Received: 8 November 2022 Accepted: 2 December 2022 Published: 11 January 2023 Abstract: Ulcerative colitis (UC), an inflammatory intestinal disease, is a growing epidemic affecting people worldwide and requires the development of effective therapeutic drugs. In this study, the effect of 23-hydroxybetulinic acid (23-HBA), a compound isolated from the traditional herb Pulsatilla chinensis (Bunge) Regel, on experimental UC was studied. C57BL/6J male mice were administrated with 3% dextran sodium sulfate (DSS) in drinking water to establish the UC model. 23-HBA was orally administrated at either 3.75, 7.5, or 15 mg/kg for 6 days. Mesalazine was used as a positive control. Examination of the body weight, colon length, disease activity index (DAI), histopathology examination, inflammatory cytokines, oxidative stress, and protein expression was performed. The pathological changes were examined with hematoxylin and eosin (H&E) and Aixian blue-glycogen (AB-PAS) staining. In cultured RAW 264.7 cells, the effects of 23-HBA on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and oxidative stress were analyzed. Compared with the colitis model, 23-HBA treatment significantly increased the body weight and colon length and decreased the DAI score. Pathological staining showed that 23-HBA mitigated the damage in intestinal structures, the increase in inflammatory cell infiltration, the increase in submucosa edema, and the decrease in goblet cell number. Furthermore, 23-HBA decreased IL-1β, IL-6, and MDA levels in the colon tissues. In addition, 23-HBA inhibited the protein expressions of COX-2, iNOS, and NF-κB p65 both in the colon tissues and in LPS-stimulated RAW 264.7 cells. In conclusion, these results showed that 23-HBA alleviated DSS-induced acute UC in mice and inhibited LPS-stimulated inflammation in RAW 264.7 cells possibly mediated by regulating the NF-κB pathway.

Study on the preparation of EGCG-γ-Cyclodextrin inclusion complex and its drug-excipient combined therapeutic effects on the treatment of DSS-induced acute ulcerative colitis in mice

In this study, γ-cyclodextrins (γ-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-γ-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of γ-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-γ-IC effectively inhibited the secretions of NO, TNF-α, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-γ-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1β, IL-6, and TNF-α in serum, and restoring MPO, GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-γ-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and γ-CD alone. Therefore, EGCG-γ-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.

Preventive effect of Atractylodis Rhizoma extract on DSS-induced acute ulcerative colitis through the regulation of the MAPK/NF-κB signals in vivo and in vitro

Ethnopharmacological relevanceAtractylodes lancea (Thunb.) DC. is traditionally used as a folk medicine for treating gastrointestinal diseases in China. Nevertheless, the effect and mechanisms of its anti-inflammatory activity on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) have not yet been fully investigated.Aim of the study: This study aimed to explore the therapeutic effect and underlying molecular mechanisms of Ethanolic Extract of Atractylodis Rhizoma (EEAR) on DSS-induced UC mice and LPS-induced RAW264.7 cells. Materials and methodsThe EEAR was obtained and then analyzed by HPLC analysis. The protective effect of EEAR on DSS-induced UC was evaluated by weight loss, disease activity index (DAI) score, spleen index, goblet cell loss, colon length shortening, myeloperoxidase (MPO) activity and pathological changes. The level of inflammatory cytokines were detected by immunohistochemistry (IHC) and RT-PCR analysis. The expressions of the tight junction (TJ, such as ZO-1, Occludin) proteins and the target proteins in mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) were determined by western blotting analysis. ResultsEEAR significantly attenuated the symptoms of UC, suppressed the colon MPO activity, and increased the goblet cell loss. In addition, EEAR could significantly increase the expression of TJs in UC mice. Meanwhile, EEAR treatment could reduce the levels of inflammatory cytokines and inhibit the phosphorylation of MAPK and NF-κB signaling pathways in UC mice and in LPS-induced RAW264.7 cells. ConclusionOur results indicated that EEAR ameliorated DSS-induced UC by inhibiting the inflammatory response and maintaining the intestinal barrier function via modulation of MAPK/NF-κB pathways, thus, EEAR might be a promising therapeutic candidate for UC therapy.

Apple Polyphenols Extract (APE) Alleviated Dextran Sulfate Sodium Induced Acute Ulcerative Colitis and Accompanying Neuroinflammation via Inhibition of Apoptosis and Pyroptosis.

The main aim of this study was to investigate the potent anti-apoptosis and anti-pyroptosis effects of apple polyphenols extract (APE) on dextran sulfate sodium model group (DSS)-induced acute ulcerative colitis (UC) and the protective effect of APE against acute UC-related neuroinflammation and synapse damage. Forty-three C57BL/6 male mice were randomly divided into a control group (CON), a 3% DSS model group (DSS), a 500 mg/(kg·bw·d) APE group (HAP), and a 125 (LD) or 500 (HD) mg/(kg·bw·d) APE treatment concomitantly with DSS treatment group. The results showed that APE significantly ameliorated DSS-induced acute UC through inhibiting intestinal epithelial cell (IEC) apoptosis and the Caspase-1/Caspase-11-dependent pyroptosis pathway, with increased BCL-2 protein expression and decreased protein levels of NLRP3, ASC, Caspase-1/11, and GSDND. Furthermore, APE significantly reduced acute UC-related neuroinflammation and synapse damage, supported by decreased mRNA levels of hypothalamus Cox-2 and hippocampus Gfap and also increased the mRNA levels of hypothalamus Psd-95. The increased protein expression of ZO-1 and Occludin improved the intestinal barrier integrity and improved the function of goblet cells by upregulating the protein level of MUC-2 and TTF3 accounted for the beneficial effects of APE on UC-associated neuroinflammation. Therefore, APE might be a safe and effective agent for the management of acute 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.

Pharmacoproteomics reveals the mechanism of Chinese dragon's blood in regulating the RSK/TSC2/mTOR/ribosome pathway in alleviation of DSS-induced acute ulcerative colitis

Ethnopharmacological relevanceChinese dragon's blood (CDB), a crude drug extracted from Dracaena cochinchinensis (Lour.) S.C. Chen, has been historically applied for the treatment of various diseases, including ulcerative colitis (UC). Unfortunately, the underlying molecular mechanism remains unclear. Materials and methodsIn this paper, the effects of CDB treatment on a mouse model of acute UC and proteomic variation in colonic tissue were investigated. The acute UC model in Balb/c mice was induced by administration of 2.5% (wt/vol) dextran sulfate sodium (DSS) in drinking water for 8 days. After the mice with UC were intragastrically administered CDB and intraperitoneally injected with rapamycin (RAPA, a specific inhibitor of mTORC1), the disease activity index (DAI) and histopathological score were recorded. An isobaric tags for relative and absolute quantification (iTRAQ) based LC-MS/MS proteomic technique was adopted to identify the differentially expressed proteins (DEPs) in colonic tissue. Bioinformatics analysis was used to discover the molecular functions and pathways of the DEPs. Finally, Western blot analysis and immunohistochemistry were used to verify the protein expression. ResultsThe results showed that CDB treatment significantly ameliorated the symptoms and intestinal damage in acute UC, while RAPA treatment led to severe symptoms and intestinal damage. A total of 489 DEPs were reversed in the control check (CK) group and the CDB group. Most DEPs were enriched in the structural constituents of ribosomes and the ribosome pathway. CDB treatment significantly upregulated the expression of the mTOR, p-mTOR and p70S6K proteins and downregulated the expression of the Akt, p-Akt, and p4EBP1 proteins. However, RAPA treatment, unlike CDB, did not return the levels of mTOR, Akt, and their phosphorylated forms to nearly normal. ConclusionsIn conclusion, the dysfunction of the mTOR/ribosome pathway resulting in the inhibition of ribosome synthesis played an important role in the development of acute UC in mice, and CDB, but not RAPA, was an alternative drug for the treatment of acute UC by enhancing ribosome synthesis via the mTOR/ribosome pathway and further promoting protein synthesis.

Extra virgin olive oil and flaxseed oil have no preventive effects on DSS-induced acute ulcerative colitis.

The aim of this study was to evaluate the preventive effects of extra virgin olive oil (EVOO) or flaxseed oil (FO) on dextran sodium sulfate (DSS)-induced acute ulcerative colitis in female mice. Eighty C57BL/6J mice of 8-weeks-old were divided in four groups: Control (SO), 10%EVOO, 10%FO and 5%EVOO+5%FO. The oils were given through the AIN-93M diet. After 30 days, animals were divided in four more groups, in which half received 3%DSS in water for 5 days. Body weight loss, bleeding and stool consistency were verified for the Disease Activity Index (DAI). Animals were euthanized and their colon and spleen weighted and measured. Histopathological analysis, the concentrations of TNF-α, IL-1β, and IL-10 and the iNOS expression were evaluated in the colon samples. Animals that received DSS presented with elevated disease activity index values; increased colon weight-to-length ratio; augmented leukocyte infiltration into the lamina propria and submucosa; and increased production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, and greater inducible nitric oxide synthase expression in the distal colon. Individually or in combination, the oils were not able to reverse or mitigate any of the DSS-induced symptoms or damage. Additionally, the group of animals treated with DSS and supplemented with FO displayed increased spleen weight-to-body weight ratio, and the group that received a combination of EVOO and FO presented increased TNF-α levels compared with the respective control group. Consumption of large amounts of EVOO and FO as a treatment for or prevention against ulcerative colitis could potentially elicit unwanted adverse effects.

Effect of cystatin from Schistosoma japonicum on DSS - induced ulcerative colitis in mice

To investigate the effect of cysteine protease inhibitor derived from Schistosoma japonicum (SjCystatin) on dextran sodium sulfate (DSS)-induced acute ulcerative colitis in mice. Eighteen C57BL/6 mice were randomly divided into three groups: a control group treated with PBS (Group A), a DSS-induced-colitis group treated with PBS (Group B), and a DSS-induced-colitis group treated with SjCystatin (Group C). Colitis was induced in mice by giving 3% DSS orally for 7 days. During this period, the mice were daily injected with 10 μg of SjCystatin or PBS only as a control intraperitoneally. The mice were monitored daily for their clinical manifestations and given scores based on disease activity index (DAI). The severity of colonic inflammation was monitored by the macroscopic score and pathological change. The cytokine profile including TNF-α, IL-4, IL-6 and IL-10 in the supernatants of colon homogenate was detected by ELISA. Compared with Group A (0.50 ± 0.28), the DAI score increased significantly in Group B (9.30 ± 1.30) (F = 86.86, P < 0.01), with remarkable pathological damages seen in colon tissues. and the levels of TNF-α and IL-6 were (321.33±67.01) and (403.58 ±180.51) pg/mL. The DAI score significantly reduced in Group C (6.67±1.57) as compared to Group B (F = 86.86, P < 0.01), with improvements in the macroscopic and microscopic pathology in mouse colon specimens. As compared to Group B, the levels of TNF-α [(188.14 ± 40.14) pg/mL] and IL-6 ([ 209.71 ± 48.47) pg/mL] significantly decreased (F = 17.46 and 9.89, both P < 0.01). SjCystatin has a significantly inhibitory effect for alleviating DSS-induced acute ulcerative colitis in C57BL/6 mice.

Extracellular Vesicles From the Helminth Fasciola hepatica Prevent DSS-Induced Acute Ulcerative Colitis in a T-Lymphocyte Independent Mode.

The complexity of the pathogenesis of inflammatory bowel disease (ulcerative colitis and Crohn’s disease) has led to the quest of empirically drug therapies, combining immunosuppressant agents, biological therapy and modulators of the microbiota. Helminth parasites have been proposed as an alternative treatment of these diseases based on the hygiene hypothesis, but ethical and medical problems arise. Recent reports have proved the utility of parasite materials, mainly excretory/secretory products as therapeutic agents. The identification of extracellular vesicles on those secreted products opens a new field of investigation, since they exert potent immunomodulating effects. To assess the effect of extracellular vesicles produced by helminth parasites to treat ulcerative colitis, we have analyzed whether extracellular vesicles produced by the parasitic helminth Fasciola hepatica can prevent colitis induced by chemical agents in a mouse model. Adult parasites were cultured in vitro and secreted extracellular vesicles were purified and used for immunizing both wild type C57BL/6 and RAG1-/- mice. Control and immunized mice groups were treated with dextran sulfate sodium 7 days after last immunization to promote experimental colitis. The severity of colitis was assessed by disease activity index and histopathological scores. Mucosal cytokine expression was evaluated by ELISA. The activation of NF-kB, COX-2, and MAPK were evaluated by immunoblotting. Administration of extracellular vesicles from F. hepatica ameliorates the pathological symptoms reducing the amount of pro-inflammatory cytokines and interfering with both MAPK and NF-kB pathways. Interestingly, the observed effects do not seem to be mediated by T-cells. Our results indicate that extracellular vesicles from parasitic helminths can modulate immune responses in dextran sulfate sodium (DSS)-induced colitis, exerting a protective effect that should be mediated by other cells distinct from B- and T-lymphocytes.

Therapeutic roles of polysaccharides from Dendrobium Officinaleon colitis and its underlying mechanisms

Polysaccharide, as a promising candidate to meet the medication requirement of ulcerative colitis (UC), is increasingly attracting extensive interest. Dendrobium officinale has been widely used to treat gastrointestinal sickness in the clinical treatment of Traditional Chinese Medicine. However, it remains largely unknown whether polysaccharides (DOPS) from Dendrobium officinale can treat UC. The purpose of this paper is to confirm therapeutic action of DOPS to UC and explored its underlying mechanisms. We noted that DOPS could dramatically improve clinical signs and symptoms, decrease mortality, alleviate colonic pathological damage, and reestablish the balance of pro- and anti-inflammatory cytokines in DSS-induced acute UC mice. Moreover, DOPS treatment could also markedly suppress the activation of NLRP3 inflammasome and β-arrestin1 in vivo and in vitro. This study showed that DOPS possesses appreciable therapeutic effect to treat experimental acute UC mice. Its mechanism could be related to inhibition of NLRP3 inflammasome and β-arrestin1 signaling pathways.

Therapeutic effect of anti-CXCL1 neutralizing antibody on acute ulcerative colitis in mice

To evaluate the therapeutic effect of CXCL1 monoclonal antibody on dextra sulfate sodium (DSS)-induced acute ulcerative colitis (UC) in mice, and to elucidate its effect on the expressions of TNF-α, IFN-γ, IL-17 and IL-10 as well as neutrophil infiltration. Methods: Female BALB/c mice were randomly divided into a normal group (DSS-), a disease group (DSS+saline), an anti-CXCL1 antibody group (DSS+anti-CXCL1 Ab) and a treatment control group (DSS+IgG Ab). The DSS+saline, DSS+anti-CXCL1 Ab and DSS+anti-CXCL1 Ab groups were given 3.5% DSS solution as drinking water to induce acute intestinal inflammation, while the normal control was given distilled water freely. The DSS+anti-CXCL1 Ab mice were intraperitoneal injected with anti-CXCL1 Ab (4 mg/kg) on the 3rd and 6th day. Same amount of rat IgG Ab was given in the DSS+IgG Ab group. The normal group and the disease group were injected with 0.9% sodium chloride solution. The value of disease activity index (DAI) and the injury of colorectal tissue were measured. The levels of TNF-α, IFN-γ, IL-10 and IL-17 in colonic tissues of mice were detected by RT-PCR. Myeloperoxidase (MPO), a specific marker of neutrophils was measured by immunohistochemistry. Results: Compared with the normal control group, DAI score and colorectal injury score in the disease group were significantly increased, but the DAI and colorectal in the mice with acute ulcerative colitis tissue damage score were significantly reduced after anti-CXCL1 Ab intervention. Compared with the normal control group, mRNA levels of TNF-α, IFN-γ and IL-17 in the colorectal tissues were significantly elevated (P<0.05) in the disease group while the IL-10 was decreased; these effects were attenuated by anti-CXCL1 Ab intervention (P<0.05). Immunohistochemistry showed that the infiltration of neutrophils (MPO+) in the colon tissue was significantly increased in the disease group, while the anti-CXCL1 Ab treatment could significantly reduce the neutrophil infiltration in colon tissue (P<0.05). Conclusion: Anti-CXCL1 Ab relieves the progression of DSS-induced acute ulcerative colitis by suppressing proinflammatory expression and neutrophil infiltration.

SXP-RAL Family Filarial Protein, rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis.

Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP-RAL family protein of Wuchereria bancrofti i.e. rWbL2 protein in DSS induced inflammatory ulcerative colitis in a mouse model. Prior treatment of rWbL2, followed by induction of colitis, showed significantly reduced disease severity as indicated by the decreased disease manifestations and improved macroscopic and microscopic inflammation. This preventive effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-17 by the splenocytes of treated mice. From this study, it can be envisaged that pretreatment with filarial protein, rWbL2, can prevent the establishment of ulcerative colitis in BALB/c mice. The underlying immunological mechanism may involve the up-regulation of Th2 immune response with down-regulation of Th1 response.

Protective effects of Huangqin Decoction against ulcerative colitis and associated cancer in mice.

Individuals with ulcerative colitis (UC) are at a high risk for developing colorectal cancer (CRC). Huangqin Decoction (HQD), a traditional Chinese medicinal formula chronicled in the Shang Han Lun, is commonly used to treat gastrointestinal symptoms. However, experimental evidence for supporting the clinical practice is lacking. This study used modern biomedical approaches to investigate the protective/preventive effects of HQD in dextran sulfate sodium (DSS)-induced acute/chronic UC and azoxymethane (AOM)/DSS-induced CRC in mice. HQDs were prepared in 4 different ways: HQD-1 and HQD-2 were prepared in boiling water, whereas HQD-3 and HQD-4 were prepared in heated ethanol (70%). For HQD-1 and HQD-3, the 4 constituent herbs were processed together, whereas for HQD-2 and HQD4, these herbs were processed individually and then combined. The mice were administered 9.1 g/kg HQD via oral gavage daily. HQD-1 significantly inhibited DSS-induced acute UC, whereas HQD-3 and HQD-4 exhibited mild ameliorative effects; but HQD-2 had no protective effect and resulted in a higher mortality rate. This higher mortality rate may be due to the greater abundance of baicalein and wogonin in HQD-2 than HQD-1. Furthermore, HQD-1 protected against DSS-induced chronic UC and significantly inhibited AOM/DSS-induced CRC in mice. HQD-1 also inhibited the production of inflammatory cytokines and increased antioxidant capacity both in chronic DSS and AOM/DSS treated mice. Overall, HQD-1 inhibits the development of acute/chronic colitis and prevents colitis-associated CRC, possibly by inhibiting inflammation and preventing oxidative stress induced cellular damage.

The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-κB pathway.

Ulcerative colitis (UC) is a chronic inflammatory intestinal disease. It is necessary to find out new effective drugs for UC. In our study epicatechin extracted from grape seed by our institute for the first time could treat UC effectively. Then anti-UC mechanisms of epicatechin were elucidated in vivo and in vitro. Dextran sulfate sodium (DSS)-induced acute UC mice model was used to evaluate the activity of epicatechin and its properties against UC. Then its anti-inflammatory and antioxidant effects were evaluated as follows: the concentrations of TNF-α and IL-6 in the colon supernatants were determined by ELISA. NO and MPO were assayed by Griess method and commercial kit respectively. NF-κB were determined by NF-κB-Dependent Reporter Gene Expression Assay and Western Blotting respectively. Antioxidant factors such as SOD, MDA, GSH-Px and CAT were also measured in colon tissues and cell supernatant stimulated by LPS respectively. In C57BL/6J mice model with DSS-induced UC, epicatechin was able to decrease the disease activity index and colon macroscopic damage index scores, reduce body weight loss, and significantly relieve colon contracture and crypt damage. TNF-α, IL-6, NO, MPO and MDA were reduced in the mice administered epicatechin, whereas antioxidant enzymes showed increased activity in epicatechin-treated mice and cell line respectively. Furthermore, inhibition effect on NF-κB activation by epicatechin were demonstrated in vivo and in vitro. Epicatechin has inhibitory effect on DSS-induced acute UC. This effect is mainly due to its antioxidant effect and the inhibition of inflammatory molecules related to NF-κB pathway.

Effects of fish scale collagen peptide on an experimental ulcerative colitis mouse model

The aim of this study was to understand the effects of fish scale collagen peptide (SC) on an experimental ulcerative colitis (UC) mouse model. SC shortened colon length, increased colon weight/length ratio, and ameliorated histological tissue injury in dextran sulfate sodium (DSS)-induced acute UC mice. SC suppressed inflammation in acute UC by decreasing myeloperoxidase-dependent activation of inflammatory cells such as leukocytes. SC suppressed the activation of nuclear factor-kappa B (NF-κB) in colon and serum monocyte chemotactic protein-1 in the DSS-induced acute UC mouse model. Gelatin, on the other hand, did not suppress clinical symptoms, colon inflammation, and colon fibrosis in DSS-induced acute UC. These results revealed that SC has anti-inflammatory effects in the DSS-induced acute UC model. Our results indicate that SC could be a new functional food for patients with inflammatory bowel disease.

Systemic Responses of Mice to Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis Using 1H NMR Spectroscopy

The interplay between genetic mutation and environmental factors is believed to contribute to the etiology of inflammatory bowel disease (IBD). While focused attention has been paid to the aforementioned research, time-specific and organ-specific metabolic changes associated with IBD are still lacking. Here, we induced acute ulcerative colitis in mice by providing water containing 3% dextran sulfate sodium (DSS) for 7 days and investigated the metabolic changes of plasma, urine, and a range of biological tissues by employing a (1)H nuclear magnetic resonance (NMR)-based metabonomics approach with complementary information on serum clinical chemistry and histopathology. We found that DSS-induced acute ulcerative colitis leads to significant elevations in the levels of amino acids in plasma and decreased levels in the membrane-related metabolites and a range of nucleotides, nucleobases, and nucleosides in the colon. In addition, acute-colitis-induced elevations in the levels of nucleotides in the liver were observed, accompanied by reduced levels of glucose. DSS-induced acute colitis also resulted in increased levels of oxidized glutathione and attenuated levels of taurine in the spleen. Furthermore, acute colitis resulted in depletion in the levels of gut microbial cometabolites in urine along with an increase in citric acid cycle intermediates. These findings suggest that DSS-induced acute colitis causes a disturbance of lipid and energy metabolism, damage to the colon and liver, a promoted antioxidative and anti-inflammatory response, and perturbed gut microbiotal communities. The information obtained here provided details of the time-dependent and holistic metabolic changes in the development of the DSS-induced acute ulcerative colitis, which could be useful in discovery of novel therapeutic targets for management of IBD.