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?-Sitosterol and stigmasterol ameliorate dextran sulfate sodium-induced colitis in mice fed a high fat Western-style diet.

ABSTRACT: Phytosterols, the plant analogues of cholesterol, widely occur in the human diet. In this study, we investigated and compared the effects of stigmasterol and ?-sitosterol (both with purities ?95%) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J male mice fed a high fat Western-style diet. Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium. Both ?-sitosterol and stigmasterol significantly inhibited colon shortening, lowered fecal hemoglobin content, and reduced the severity of colitis in the middle and distal colon (p < 0.05). These phytosterols also significantly suppressed the activation of nuclear factor-kappa B. They also significantly decreased colony stimulating factor-1 and the nuclear translocation of inflammatory master regulator nuclear factor-kappa B. Stigmasterol significantly lowered the colonic inflammation score and the expression of cyclooxygenase-2 and colony stimulating factor-1, while ?-sitosterol was less or not effective. These results suggest that dietary intake of stigmasterol and ?-sitosterol ameliorates colitis. Such activities of stigmasterol and ?-sitosterol in humans remain to be investigated.

SUBMITTER: Feng S

PROVIDER: S-EPMC5875920 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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β-Sitosterol and stigmasterol ameliorate dextran sulfate sodium-induced colitis in mice fed a high fat Western-style diet.

Feng Simin S Dai Zhuqing Z Liu Anna A Wang Hong H Chen Jayson J Luo Zisheng Z Yang Chung S CS

Food & function 20171101 11

Phytosterols, the plant analogues of cholesterol, widely occur in the human diet. In this study, we investigated and compared the effects of stigmasterol and β-sitosterol (both with purities ≥95%) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J male mice fed a high fat Western-style diet. Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium. Both β-sitosterol and stigmasterol significantly inhibited colon shorte ...[more]

PMID: 29034917

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Project description:BACKGROUND:G 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. METHODS:Colitis 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. RESULTS:GPR35-/- 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-1?, CXCL1, CXCL2, CCL2, HMGB1, TGF?1, TGF?3, 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. CONCLUSIONS:Our 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

?-Sitosterol and stigmasterol ameliorate dextran sulfate sodium-induced colitis in mice fed a high fat Western-style diet.

Publications

β-Sitosterol and stigmasterol ameliorate dextran sulfate sodium-induced colitis in mice fed a high fat Western-style diet.

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