Mechanism and therapeutic effects of Saccharomyces boulardii on experimental colitis in mice

Abstract Background and Aims Alteration to both the structures and functions of mesenteric lymphatic vessels is a typical hallmark of Crohn’s disease [CD]. Dysfunctional lymphatics was observed in patients with both CD and experimental colitis, suggesting mesenteric lymphatics could be potential therapeutic targets. This study aimed to develop a nano-delivery system which can enhance drug delivery in mesenteric lymphatic tissue [MLT] and evaluate the therapeutic effects in Crohn’s colitis. Methods We designed a mesoporous silica nanoparticle [MSN] conjugated with long-chain fatty acid [LMSN] and covered with enteric coating [ELMSN] which can be specifically transported via the mesenteric lymphatic system. The therapeutic efficacy of laquinimod-loaded nanoparticles [LAQ@ELMSN] was evaluated in the well-established interleukin [IL]-10−/− spontaneous experimental colitis. Results ELMSNs induced sustainable drug release that markedly increased drug concentration in MLT. In experimental colitis, the lymphatics-targeting drug delivery system suppressed lymphangitis and promoted lymphatic drainage. The downregulation of pro-inflammatory cytokines and the downstream NF-κB-related proteins efficiently inhibited lymphangiogenesis and restored tight junctions of mesenteric lymphatic vessels [MLVs]. LAQ@ELMSN showed a superior therapeutic effect in ameliorating intestinal inflammation compared with free drug administration. Alteration of gut microbiota and metabolites in experimental colitis was also reversed by LAQ@ELMSN. Conclusion Our study demonstrates a convenient, orally administered drug delivery system which enhances drug release in MLT. The results confirm the contribution of the mesenteric lymphatic system to the pathogenesis of gut inflammation and shed light on the application of lymphatics-targeting drug delivery therapy as a potential therapeutic strategy for CD treatment.

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Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer

Biomedicines ◽

10.3390/biomedicines8040086 ◽

2020 ◽

Vol 8 (4) ◽

pp. 86 ◽

Cited By ~ 1

Author(s):

Sang-Hyeon Nam ◽

Jin-Kyung Kim

Keyword(s):

Colon Cancer ◽

Experimental Colitis ◽

Therapeutic Effects ◽

Mrna Levels ◽

Colon Tissue ◽

Colon Tumorigenesis ◽

Inflammatory Status ◽

Tussilago Farfara ◽

Preventive Activity ◽

Induced Apoptosis

Background: Tussilagone, a major component of Tussilago farfara L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). We injected BALB/c mice with AOM and administered 2% DSS in drinking water. The mice were given tussilagone (2.5 and 5 mg/kg body weight) and colon tissues was collected at 72 days. We used Western blotting, immunohistochemistry and real-time RT-PCR analyses to examine the tumorigenesis and inflammatory status of the colon. Results: Tussilagone administration significantly reduced the formation of colonic tumors. In addition, tussilagone treatment markedly reduced the inflammatory mediators and increased heme oxygease-1 in protein and mRNA levels in colon tissues. Meanwhile, nuclear NF-κB-positive cells were elevated and nuclear Nrf2-positive cells were demised by tussilagone treatment in colon tissues. Tussilagone also reduced cell proliferation, induced apoptosis and decreased the β-catenin expression. Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. Overall, this study indicates the potential value of tussilagone in suppressing colon tumorigenesis.

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Therapeutic effects of four molecular-weight fractions of Kurozu against dextran sulfate sodium-induced experimental colitis

The Turkish Journal of Gastroenterology ◽

10.4318/tjg.2011.0239 ◽

2011 ◽

Vol 22 (4) ◽

pp. 376-381 ◽

Cited By ~ 1

Author(s):

Toru SHIZUMA ◽

Masanobu NAGANO ◽

Akira FUJII ◽

Hidezo MORI ◽

Naoto FUKUYAMA

Keyword(s):

Molecular Weight ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Experimental Colitis ◽

Therapeutic Effects ◽

Molecular Weight Fractions

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Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

10.21203/rs.3.rs-27576/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Dingding Yu ◽

Yiming Zhao ◽

Yonghao Hu ◽

Dejun Kong ◽

Wang Jin ◽

...

Keyword(s):

Stromal Cells ◽

Tap Water ◽

Body Weight Loss ◽

Experimental Colitis ◽

Underlying Mechanism ◽

Therapeutic Effects ◽

Endometrial Regenerative Cells ◽

Tnf Α ◽

Regenerative Cells ◽

Dickkopf 1

Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1low-ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1low-ERCs) and glucocorticoid-treated ERCs (DKK1high-ERCs) were injected (1 million/mouse/day, i.v.) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1low-ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4+IL-4+Th2, CD4+CD25+FOXP3+Treg, and CD68+CD206+macrophages in spleens were also significantly upregulated in DKK1low-ERC group (p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1low-ERC group (p < 0.01 vs. other groups). Conclusions DKK1low-ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.

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The Therapeutic Efficacy of Adipose Tissue-Derived Mesenchymal Stem Cell Conditioned Medium on Experimental Colitis Was Improved by the Serum From Colitis Rats

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.694908 ◽

2021 ◽

Vol 9 ◽

Author(s):

Li-li Qi ◽

Zhe-yu Fan ◽

Hai-guang Mao ◽

Jin-bo Wang

Keyword(s):

Conditioned Medium ◽

Inflammatory Cytokines ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Experimental Colitis ◽

Sodium Sulphate ◽

Conditioned Media ◽

Therapeutic Effects ◽

Paracrine Factors ◽

Staining Methods

Adipose derived mesenchymal stem cells (AD-MSCs) have shown therapeutic potential in treatments of inflammatory bowel disease (IBD). Due to the harsh host environment and poor survival of the cells, controversy concerning the homing, proliferation and differentiation of MSCs in lesion tissue still remains. It has been reported that conditioned media from MSCs could improve the colitis, whereas the therapeutic efficiency could be significantly elevated by the stimulation of pro-cytokines. In this study, we pre-treated the adipose derived MSCs with the serum from colitis rats and then the activated conditioned media (CM-AcMSC) were collected. To compare the therapeutic effects of CM-MSC and CM-AcMSC on IBD, we constructed dextran sodium sulphate (DSS)-induced colitis rat models. The colitis was induced in rats by administrating 5% DSS in drinking water for 10 days, and the disease symptoms were recorded daily. The colon histopathological changes were observed by different staining methods (H&E and PAS). The expression levels of MUC2 and tight junctions (TJs) were determined by RT-qPCR. The levels of inflammatory cytokines were analyzed by ELISA and western blot analysis. Our findings suggested that CM-AcMSC was more effective in ameliorating the clinical features and histological damage scores. Treatment with CM-AcMSC significantly increased the expression of MUC2 and TJs and suppressed the production of pro-inflammatory cytokines in colonic tissues of colitis rats. The inhibitory effects of CM-AcMSC on inflammatory responses of colitis rats were mediated by NF-κB signaling pathway. These results suggested that pre-activation of MSCs with serum from colitis rats could promote the production of paracrine factors and improve the therapeutic effects of conditioned medium on colitis rats.

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Panax notoginseng Promotes Repair of Colonic Microvascular Injury in Sprague-Dawley Rats with Experimental Colitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4386571 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Shiying Wang ◽

Ping Tao ◽

Lei Zhao ◽

Wangjun Zhang ◽

Hongyi Hu ◽

...

Keyword(s):

Colonic Mucosa ◽

Intestinal Inflammation ◽

Experimental Colitis ◽

Panax Notoginseng ◽

Control Group ◽

Therapeutic Effects ◽

Serum Concentrations ◽

Sprague Dawley ◽

Microvascular Injury ◽

Colitis Model

To investigate the therapeutic effects of PN on intestinal inflammation and microvascular injury and its mechanisms, dextran sodium sulfate- (DSS-) or iodoacetamide- (IA-) induced rat colitis models were used. After colitis model was established, PN was orally administered for 7 days at daily dosage of 1.0 g/kg. Obvious colonic inflammation and mucosal injuries and microvessels were observed in DSS- and IA-induced colitis groups. DAI scores, serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6, and TNF-α, and expression of Rap1GAP and TSP1 proteins in the colon were significantly higher while serum concentrations of IL-4 and IL-10 and MVD in colon were significantly lower in the colitis model groups than in the normal control group. PN promoted repair of colonic mucosal injury and microvessels, attenuated inflammation, and decreased DAI scores in rats with colitis. PN also decreased the serum concentrations of VEGFA121, VEGFA165, VEGFA165/VEGFA121, IL-6, and TNF-α and increased the serum concentrations of IL-4 and IL-10, with the expression of Rap1GAP and TSP1 proteins in colonic mucosa being downregulated. The constituents of PN were identified with HPLC-DAD. To sum up, PN could promote repair of injuries of colonic mucosa and microvessels via downregulating VEGFA isoforms and inhibiting Rap1GAP/TSP1 signaling pathway.

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Effects of Guchang Capsule on Dextran Sulphate Sodium-Induced Experimental Ulcerative Colitis in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/3150651 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Baoshan Liu ◽

Tong Liu ◽

Xiaohong Wang ◽

Xin Zheng ◽

Hong Wang ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Body Weight Loss ◽

Experimental Colitis ◽

Intestinal Disease ◽

Therapeutic Effects ◽

Dextran Sulphate ◽

Chinese Materia Medica ◽

Dextran Sulphate Sodium ◽

Underlying Mechanisms

Guchang capsule (GC) is a Chinese materia medica standardized product extracted from 15 Chinese traditional medical herbs and it has been clinically used in the treatment of intestinal disease. In this study, in order to extend the research of GC in intestinal disease, we were aiming to evaluate potential effects of GC on dextran sulphate sodium- (DSS-) induced murine experimental colitis and to elucidate the underlying mechanisms. GC treatment attenuated DSS-induced body weight loss and reduced the mortality. Moreover, GC treatment prevented DSS-induced colonic pathological damage; meanwhile it inhibited proinflammatory cytokines production in colon tissues.In vitro, GC significantly reduced LPS-induced proinflammatory cytokines production via inhibiting the activation of NF-κB in macrophage cells, and the expressions of several long noncoding RNAs (lncRNAs) which were reported in regulating NF-κB signaling pathway were obviously affected by adding GC into culture medium. In conclusion, our data suggested that administration of GC exhibits therapeutic effects on DSS-induced colitis partially through regulating the expression of NF-κB related lncRNAs in infiltrating immune cells.

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