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Preclinical, Journal: Panaxynol, a bioactive component of American ginseng, targets macrophages and suppresses colitis in mice. (Pubmed Central) - Jun 19, 2020
We demonstrate here that PA effectively treats colitis in a Dextran Sulfate Sodium mouse model by targeting macrophages for DNA damage and apoptosis. This study provides additional mechanistic evidence that American ginseng can be used for conventional treatment of colitis and other diseases associated with macrophage dysfunction.
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Journal: Gadd45β promotes regeneration after injury through TGFβ-dependent restitution in experimental colitis. (Pubmed Central) - Jun 14, 2020
Gadd45β-KO mice exhibited drastically greater susceptibility to dextran sulfate sodium (DSS)-induced colitis and mortality than C57BL/6J mice...Furthermore, these results indicate that the Gadd45β-regulated TGF-β signaling pathway is involved in wound healing by enhancing epithelial restitution. These results expand the current understanding of the function of Gadd45β and its therapeutic potential in ulcerative colitis.
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Journal: Long non-coding RNA CRNDE promoted cell apoptosis by suppressing miR-495 in inflammatory bowel disease. (Pubmed Central) - Jun 12, 2020
These results expand the current understanding of the function of Gadd45β and its therapeutic potential in ulcerative colitis. Our findings demonstrated that CRNDE promoted DSS-induced colonic epithelial cell apoptosis via suppressing miR-495 and increasing SOCS1, indicating CRNDE as a novel target of treating IBD.
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Preclinical, Journal: Editing of the gut microbiota reduces carcinogenesis in mouse models of colitis-associated colorectal cancer. (Pubmed Central) - Jun 12, 2020
Restricting the bloom of Enterobacteriaceae decreased intestinal inflammation and reduced the incidence of colonic tumors in two models of CAC, the azoxymethane/dextran sulfate sodium colitis model and azoxymethane-treated, Il10-deficient mice. We conclude that metabolic targeting of protumoral Enterobacteriaceae during chronic inflammation is a suitable strategy to prevent the development of malignancies arising from gut microbiota dysbiosis.
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Journal: Hydrogen sulfide protects against DSS-induced colitis by inhibiting NLRP3 inflammasome. (Pubmed Central) - Jun 10, 2020
In addition, the NLRP3 inflammasome is a key player in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis...Furthermore, the inhibitory effect of HS is due to a reduction in reactive oxygen species (ROS) generation and partly dependent on the disruption of nuclear erythroid 2-related factor-2 (Nrf2) activation. Collectively, our study confirms that HS exerts its protective effect on DSS-induced mouse colitis at least partly by inhibiting the activation of NLRP3 inflammasome pathway.
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Preclinical, Journal, Myeloid-derived suppressor cells: Lactoferrin-induced myeloid-derived suppressor cell therapy attenuates pathologic inflammatory conditions in newborn mice. (Pubmed Central) - Jun 10, 2020
In addition to affecting NEC, LF-MDSCs demonstrated potent ability to control ovalbumin-induced (OVA-induced) lung inflammation, dextran sulfate sodium-induced (DSS-induced) colitis, and concanavalin A-induced (ConA-induced) hepatitis. These results suggest that cell therapy with LF-MDSCs may provide potent therapeutic benefits in infants with various pathological conditions associated with dysregulated inflammation.
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Preclinical, Journal: Optical coherent tomography to evaluate the degree of inflammation in a mouse model of colitis. (Pubmed Central) - Jun 6, 2020
In this study, a dextran sulfate sodium colitis model was developed, and intestinal histological damage scores measured the degree of inflammation in colitis...Parameters based on morphological changes in OCT images and HE sections were significant indexes for evaluating the degree of inflammation in colitis. OCT images have advantages for future clinical applications in situ, including noninvasiveness and real-time imaging.
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Journal: Graphene quantum dots as anti-inflammatory therapy for colitis. (Pubmed Central) - Jun 6, 2020
Here, GQDs are intraperitoneally injected to dextran sulfate sodium (DSS)-induced chronic and acute colitis model, and its efficacy has been confirmed...Moreover, GQDs switch the polarization of macrophages from classically activated M1 to M2 and enhance intestinal infiltration of regulatory T cells (T). Therefore, GQDs effectively attenuate excessive inflammation by regulating immune cells, indicating that they can be used as promising alternative therapeutic agents for the treatment of autoimmune disorders, including IBDs.
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Preclinical, Journal, IO Biomarker: The effects and mechanisms of myeloid differentiation protein 2 on intestinal mucosal permeability in mice with chronic colitis. (Pubmed Central) - Jun 5, 2020
Briefly, a chronic colitis mouse model was established by the administration of dextran sulfate sodium (DSS) in transgenic mice of MD2 overexpression (Transgenic, MD2-Tg) and C57BL/6 wild-type mice (MD2-WT)...After MD2 silencing, the apoptotic level was decreased, the value of transepithelial electrical resistance was increased, the permeability of intestinal mucosa was decreased, the cellular expression levels of MD2, MyD88, TLR4, and HMGB1 were decreased, while the expression levels of tight junction proteins, occludin and claudin-1 were increased. MD2 could aggravate the destruction of intestinal mucosa in chronic colitis through the HMGB1-TLR4-MyD88 pathway.
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Journal: Daphnetin ameliorates experimental colitis by modulating microbiota composition and T/T17 balance. (Pubmed Central) - Jun 5, 2020
Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice...More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and T/T17 balance.
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Journal: Activation of NLRX1 by NX-13 Alleviates Inflammatory Bowel Disease through Immunometabolic Mechanisms in CD4 T Cells. (Pubmed Central) - Jun 4, 2020
Oral treatment with NX-13 alleviates disease severity, colonic leukocytic infiltration, and cytokine markers of inflammation in three mouse models of IBD (dextran sulfate sodium, Mdr1a, and CD45RB adoptive transfer)...NX-13 activates NLRX1 to mediate a resistance to both inflammatory signaling and oxidative stress in mouse models and human primary cells from ulcerative colitis patients with effects on NF-κB activity and oxidative phosphorylation. NX-13 is a promising oral, gut-restricted NLRX1 agonist for treating IBD.
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Journal: Intranasal Mycobacterium vaccae administration prevents stress-induced aggravation of dextran sulfate sodium (DSS) colitis. (Pubmed Central) - May 31, 2020
However, the effects of M. vaccae on stress-induced anxiety are difficult to interpret, as CSC in the current experimental setting did not reliably increase anxiety-related behavior. Taken together, these data broaden the framework for developing bioimmunoregulatory approaches, based on the administration of microorganisms with anti-inflammatory and immunoregulatory properties, for the prevention of stress-related disorders.
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Preclinical, Journal: Barbaloin Attenuates Mucosal Damage in Experimental Models of Rat Colitis by Regulating Inflammation and the AMPK Signaling Pathway. (Pubmed Central) - May 29, 2020
Our study evaluated its efficacy against dextran sulfate sodium (DSS)-induced colitis in rats...Additionally, si-RAN-induced knockdown, and overexpression assay showed that barbaloin could inhibit the UC-enhanced MLCK signaling pathway by activating the AMPK signaling pathway. CONCLUSIONS Barbaloin can effectively inhibit inflammation and reverse epithelial barrier function to protect against UC, possibly via activation of the AMPK signaling pathway.
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Journal: Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production. (Pubmed Central) - May 29, 2020
Thus, we asked whether IVIg-treated macrophages or IVIg could reduce intestinal inflammation in mice during dextran sulfate sodium (DSS)-induced colitis by inducing macrophage IL-10 production in vivo...Together, our data demonstrate a novel, in vivo mechanism of action for IVIg. IVIg-treated macrophages or IVIg could be used to treat people with intestinal inflammation and may be particularly useful for people with inflammatory bowel disease, who are refractory to therapy.
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Biomarker, Journal: Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation. (Pubmed Central) - May 26, 2020
Syndecan-2 expression was up-regulated predominantly in the proximal colon of dextran sulfate sodium-induced colitis mice...Together, these data suggest that acute inflammation induces syndecan-2 expression predominantly in the proximal colon via IL-17A-IL-17RA signaling during the early stage of the inflammatory response and that proximal colonic syndecan-2 might be a biomarker for acute inflammation.-Hong, H., Song, H.-K., Hwang, E. S., Lee, A. R., Han, D. S., Kim, S.-E., Oh, E.-S. Up-regulation of syndecan-2 in proximal colon correlates with acute inflammation.
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Preclinical, Journal: Aquaporin 4 deficiency alleviates experimental colitis in mice. (Pubmed Central) - May 23, 2020
) mice by oral administration of dextran sulfate sodium (DSS)...These results suggested for the first time that AQP4 deficiency alleviates experimental colitis in mice. Our study helps to understand the pathogenesis of inflammatory bowel diseases, and blocking AQP4 may represent a novel therapeutic approach for ulcerative colitis.-Wang, L., Tang, H., Wang, C., Hu, Y., Wang, S., Shen, L. Aquaporin 4 deficiency alleviates experimental colitis in mice.
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Journal: Caffeic Acid Phenethyl Ester Prevents Colitis-Associated Cancer by Inhibiting NLRP3 Inflammasome. (Pubmed Central) - May 22, 2020
Here, we aimed to evaluate the anti-inflammatory effect of caffeic acid phenethyl ester (CAPE) on bone marrow-derived macrophages (BMDMs), THP-1 cells, and azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon cancer mouse model...Altogether, our findings demonstrate that CAPE prevents CAC by post-transcriptionally inhibiting NLRP3 inflammasome. Thus, CAPE may be an effective candidate for reducing the risk of CAC in patients with inflammatory bowel disease.
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Journal: Neurotrophic factor GDNF regulates intestinal barrier function in inflammatory bowel disease. (Pubmed Central) - May 21, 2020
Challenge of Caco2 cells and enteroids with proinflammatory cytokines as well as dextran sulfate sodium-induced (DSS-induced) colitis in C57Bl/6 mice led to impaired IEB function with reduced DSG2 mediated by p38 MAPK-dependent phosphorylation of cytokeratins...GDNF attenuates inflammation-induced impairment of IEB function caused by the loss of DSG2 through p38 MAPK-dependent phosphorylation of cytokeratin. The reduced GDNF in patients with IBD indicates a disease-relevant contribution to the development of IEB dysfunction.
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Preclinical, Journal: Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota. (Pubmed Central) - May 20, 2020
We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.
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Preclinical, Journal: Sweet Olive Extract Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice. (Pubmed Central) - May 20, 2020
The suppressive effects on myeloperoxidase expression and lower histopathology scores (including neutrophil infiltration) for the colon were also found. These findings suggest that OFE exerts anti-inflammatory effect on DSS-induced colitis.
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Journal: Alginate/Chitosan microparticles for gastric passage and intestinal release of therapeutic protein nanoparticles. (Pubmed Central) - May 19, 2020
We have previously shown that a Salmonella effector enzyme, AvrA, delivered by NPs is capable of modulating inflammatory signals in a murine dextran sulfate sodium (DSS) colitis model...Oral administration of AvrA NPs encapsulated in alginate/chitosan MPs delivered protein to intestinal epithelia and reduced clinical and histological scores of inflammation in a murine DSS-induced colitis model. Altogether, NPs in alginate/chitosan MPs are a potential oral delivery vehicle for protein therapeutics.
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Journal: Cancer testis antigen 55 deficiency attenuates colitis-associated colorectal cancer by inhibiting NF-κB signaling. (Pubmed Central) - May 19, 2020
We discovered that Ct55 deficiency alleviated inflammatory responses, decreased cell proliferation and colitis-associated tumorigenesis in an azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model...Notably, inhibition of IKK abolished the positive effect of CT55 on NF-κB activation. Collectively, our findings strongly indicate that CT55 deficiency suppresses the development of CAC and that the CT55-TNF-α-induced NF-κB axis may represent a promising target for CAC therapy.
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Journal: Anti-inflammatory properties of uvaol on DSS-induced colitis and LPS-stimulated macrophages. (Pubmed Central) - May 16, 2020
We investigated anti-Inflammatory effects on dextran sulfate sodium (DSS)-induced colitis mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells...venetum leaf contains uvaol and uvaol has potent anti-inflammatory effects on DSS-induced experimental colitis and LPS-stimulated RAW264.7 macrophage cells. These results suggest uvaol is a prospective anti-inflammatory agent for colonic inflammation.
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Preclinical, Journal: The effect of 6-gingerol on inflammatory response and Th17/Treg balance in DSS-induced ulcerative colitis mice. (Pubmed Central) - May 14, 2020
In this study, a dextran sulfate sodium (DSS)-induced colitis mouse model was established, and the effects of 6-gingerol on cytokines and the balance of Th17/Treg cells were observed usingserial assays, including enzyme-linked immunosorbent assay (ELISA), quantitative real time-polymerase chain reaction (qPCR), and Western blotting...Furthermore, 6-gingerol could significantly (P<0.05) inhibit the up-regulation of RORγT mRNA and protein, and the down-regulation of FOXP3 mRNA and protein induced by DSS, which is similar to the effect of mesalazine. 6-gingerol showed efficacy in the treatment of DSS-induced UC in mice, by regulating the cell balance of Th17/Treg, and by relieving inflammatory responses both systematically and locally.
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Journal: LL202 ameliorates colitis against oxidative stress of macrophage by activation of the Nrf2/HO-1 pathway. (Pubmed Central) - May 13, 2020
The results showed that LL202 decreased the proinflammatory cytokine expression and regulated colonic oxidative stress by activating the Nrf2/HO-1 pathway. In conclusion, our study showed that LL202 exerts an anti-inflammatory effect by enhancing the antioxidant capacity of the Nrf2/HO-1 pathway to macrophages.
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Journal: Syringin protects against colitis by ameliorating inflammation. (Pubmed Central) - May 13, 2020
The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.
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Journal: Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon-Soluble Capsule against Ulcerative Colitis. (Pubmed Central) - May 10, 2020
The IL-17 signaling pathway activated by infectious gastrointestinal microbes and predicted by the network analysis to be a major pathway modulated by CSCC against UC was studied in a dextran sulfate sodium-induced colitis model...Rectal administration of CSCC led to microbiota regulation with a significant correlation between suppression of Verrucomicrobiaceae and Ruminococcaceae, as well as the elevation of Lactobacillaceae, and CSCC administration via microbiome correlation heatmaps and cooccurrence network analysis at multiple time points. Thus, our study presents an effective herbal formula, CSCC, for UC treatment and explores its components and mechanisms of efficacy through the examination of gut microbiota and hallmark cytokines in the IL-17 pathway.
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Preclinical, Journal: Loss of RHBDF2 results in an early-onset spontaneous murine colitis. (Pubmed Central) - May 7, 2020
In addition, Il10 /Rhbdf2 mice failed to maintain their epithelial cell homeostasis, although the intestinal epithelial barrier of Rhbdf2 mice is intact and loss of Rhbdf2 did not significantly exacerbate sensitivity to dextran sulfate sodium-induced colitis, suggesting differences in the underlying disease pathway of intestinal inflammation in this model. Taken together, our results demonstrate a critical regulatory role for RHBDF2 in the maintenance of the unique homeostasis between intestinal microbiota and host immune responses in the gut that is dysregulated during the pathogenesis of IBD.
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PK/PD data, Preclinical, Journal: Comparative pharmacokinetics of verapamil and norverapamil in normal and ulcerative colitis rats after oral administration of low and high dose verapamil by UPLC-MS/MS. (Pubmed Central) - May 7, 2020
In this study, UC rat model was established by administration of 5% (w/v) dextran sulfate sodium, and the pharmacokinetics of verapamil and norverapamil were evaluated in normal and UC rats using UPLC-MS/MS after oral administration of 5 mg/kg and 50 mg/kg verapamil.The peak concentration (C) and the area under plasma concentration-time curves (AUC) of verapamil in UC rats after oral administration of 5 mg/kg were significantly greater (2.5 times and 2 times, respectively) than those in normal rats, but the clearance rate (Cl) was significantly lower (by 50%)...4. The findings of this study suggested that in UC patients, doses of verapamil should be decreased when low-dose verapamil was orally administrated.
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Preclinical, Journal, IO Biomarker: Lactobacillus acidophilus-Fermented Germinated Brown Rice Suppresses Preneoplastic Lesions of the Colon in Rats. (Pubmed Central) - May 7, 2020
This study investigated the preventive effect and possible mechanism of GBR fermented by Lactobacillus acidophilus (FGBR) on colorectal carcinogenesis in rats induced by 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS)...These results suggest that FGBR may inhibit preneoplastic lesions of the colon via activating the apoptotic pathway. This fermented rice product may have the potential to be developed as a novel dietary supplement for CRC chemoprevention.
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Journal: The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues. (Pubmed Central) - May 7, 2020
C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks...In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.
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