Dataset Information

Oligonol inhibits dextran sulfate sodium-induced colitis and colonic adenoma formation in mice.

ABSTRACT:

Aims

To evaluate the effects of oligonol administration on experimentally induced colitis and colonic adenoma formation.

Results

Oral administration of oligonol protected against mouse colitis induced by dextran sulfate sodium (DSS). Under the same experimental conditions, oligonol administration significantly inhibited the activation of nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 3 and expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cyclin D1 in the mouse colon. Further, oligonol inhibited azoxymethane-initiated and DSS-promoted adenoma formation in the mouse colon. Oligonol administration also attenuated lipid peroxidation (malondialdehyde) and protein oxidation (4-hydroxy-2-nonenal), thereby preventing oxidative stress-induced apoptosis of colonic epithelial cells. In vitro studies demonstrated that oligonol treatment reduced lipopolysaccharide-induced expression of interleukin (IL)-1?, tumor necrosis factor ?, il-6, cox-2, and inos in murine macrophage RAW 264.7 cells. In another study, oligonol upregulated the antioxidant gene expression in the intestinal epithelial CCD841CoN cells and in the mouse colon.

Innovation

Oligonol, an innovative formulation of catechin-type oligomers derived from the lychee fruit extract, was tested in this study for the first time to evaluate its effects on experimentally induced colitis and colonic adenoma formation in mice.

Conclusion

Oligonol is effective in protecting against DSS-induced mouse colitis and colon carcinogenesis, suggesting that this polyphenol formulation may have a potential for the amelioration of inflammatory bowel disease and related disorders.

SUBMITTER: Yum HW

PROVIDER: S-EPMC3689162 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Oligonol inhibits dextran sulfate sodium-induced colitis and colonic adenoma formation in mice.

Yum Hye-Won HW Zhong Xiancai X Park Jin J Na Hye-Kyung HK Kim Nayoung N Lee Hye Seung HS Surh Young-Joon YJ

Antioxidants & redox signaling 20130515 2

<h4>Aims</h4>To evaluate the effects of oligonol administration on experimentally induced colitis and colonic adenoma formation.<h4>Results</h4>Oral administration of oligonol protected against mouse colitis induced by dextran sulfate sodium (DSS). Under the same experimental conditions, oligonol administration significantly inhibited the activation of nuclear factor-kappa B and signal transducer and activator of transcription (STAT) 3 and expression of cyclooxygenase-2 (COX-2), inducible nitric ...[more]

PMID: 23394584

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Project description:Macrophages-involved inflammation is considered to induce the damage in various diseases. Herein, novel therapeutics inhibiting over-activation of macrophages could prove an effective strategy to prevent inflammation-related diseases. Gaudichaudione H (GH), which is a natural small molecular compound isolated from Garcinia oligantha Merr. (Clusiaceae) has previously been demonstrated its anti-cancer effects on several cancer cell lines. However, no report has been published about the anti-inflammatory effect of GH to date. This study aims to examine the anti-inflammatory effects and potential molecular mechanism of GH, and provide new insights toward the treatment of inflammation. GH inhibited nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, cytokine interleukin-6 (IL-6) and tumor necrosis factor-? (TNF-?) production, and messenger RNA (mRNA) expression to attenuate inflammatory responses in lipopolysaccharide (LPS)-induced RAW 264.7 cells or stimulated bone marrow-derived macrophages (BMDMs). GH inhibited nuclear factor-?B (NF-?B) and mitogen-activated protein kinase (MAPK) pathways, the nuclear translocation of transcription factors NF-?B and activator protein 1 (AP-1), as well as upstream signaling of the toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) pathway in stimulated macrophages. Furthermore, the result of the intracellular signaling array showed that the phosphorylation of adenosine 5'-monophosphate-activated protein kinase-? (AMPK?), proline-rich Akt substrate of 40 kDa (PRAS40), and p38 could be down regulated by GH in BMDMs, indicating that the mechanism by which GH inhibited inflammation may be also associated with the energy metabolism pathway, PRAS40-mediated NF-?B pathway, cell proliferation, apoptosis, and autophagy, etc. In addition, GH alleviated dextran sodium sulfate (DSS)-induced colitis in mice by ameliorating weight loss, stool consistency change, blood in the stool, and colon shortening. GH decreased the protein and mRNA levels of IL-6 and TNF-?, iNOS and COX-2 mRNA expression, the activation of NF-?B and MAPK pathways, the phosphorylation of AMPK? and PRAS40, histological damage, and infiltration of macrophages in the colons of mice with DSS-induced colitis. Taken together, our results support that GH exerts the anti-inflammatory effects in macrophages in vitro through regulation of NF-?B and MAPK pathways, and DSS-induced colitis mouse model in vivo. These findings suggest that GH may be a promising candidate in treating macrophage-related inflammatory disease.

Project description:BackgroundG protein-coupled receptor 35 (GPR35) is an orphan receptor and is vastly expressed in immune cells and gastrointestinal cells, suggesting the potential physiological importance of GPR35 in these cells. Here, we tested the hypothesis that the lack of GPR35 expression in the colon mucosa exacerbates the severity of dextran sulfate sodium (DSS)-induced experimental colitis in mice.MethodsColitis was induced in GPR35 wild-type (GPR35+/+) and GPR35 knockout (GPR35-/-) mice through the administration of DSS in drinking water for 5 days followed by regular facility water for 1 day. Induction of colitis was evaluated by measuring relative body weight loss, clinical illness scores, and morphological changes in the colon. Abolition of Gpr35 gene expression in the colon mucosa of GPR35-/- mice was confirmed by quantitative real-time PCR (qPCR). Gene expressions of inflammatory and tissue remodeling cytokines were detected by qPCR. Human colorectal epithelial Caco cells were transfected with siRNA against GPR35 before treated with 1% DSS in vitro. Protein expressions were measured using Western blot.ResultsGPR35-/- mice receiving DSS showed a significantly worsened colitis disease with profound loss of body weight and a considerable amount of severe clinical illness compared to GPR35+/+ mice that received DSS. The histology of colon sections from GPR35-/- mice showed extensive pathological changes including submucosal edema, diffuse ulcerations, and evidence of complete loss of crypts compared to wild-type mice. The mean histopathological score was significantly higher in GPR35-/- mice as compared to GPR35+/+ mice. The qPCR data revealed significant expression of pro-inflammatory and tissue remodeling cytokines in GPR35-/- colon mucosa, including IL-1β, CXCL1, CXCL2, CCL2, HMGB1, TGFβ1, TGFβ3, MMP1/9/12. The protein expressions of Zonula occludens-1, E-cadherin, Claudin1 were decreased upon knocking down GPR35 with or without 1% DSS treatment.ConclusionsOur experimental data suggest that lack of GPR35 resulted in worsened disease outcome in DSS-induced experimental colitis, indicating that GPR35 could play a crucial role in protecting from colonic inflammation and serve as a therapeutic target.

Dataset Information

Oligonol inhibits dextran sulfate sodium-induced colitis and colonic adenoma formation in mice.

Aims

Results

Innovation

Conclusion

Publications

Oligonol inhibits dextran sulfate sodium-induced colitis and colonic adenoma formation in mice.

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