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β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway

Authors

  • Kyung-Ah Kim,

    1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea
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  • In-Ah Lee,

    1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea
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  • Wan Gu,

    1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea
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  • Supriya R. Hyam,

    1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea
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  • Dong-Hyun Kim

    Corresponding author
    1. Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea
    • Correspondence: Professor Dong-Hyun Kim, Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul, Korea, 1, Hoegi, Dongdaemun-gu, Seoul 130-701 Korea

      E-mail: dhkim@khu.ac.kr

      Fax: +82-2-957-5030

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Abstract

Scope

β-Sitosterol, a common phytosterol, has been shown to exhibit anti-inflammatory effects. Here, we investigated the effect of β-sitosterol on high-fat diet (HFD) induced colitis in mice and on LPS-stimulated mouse intestinal macrophages.

Methods and results

C57BL/6J mice were maintained on an LFD (10 kcal% fat), an HFD (60 kcal% fat), or an HFD with β-sitosterol (20 mg/kg) administration for 8 weeks. The increased levels of body weight and epididymal fat pad weight as well as the concentrations of circulating proinflammatory cytokines and LPS in HFD mice compared with LFD mice were decreased by oral administration of β-sitosterol. The HFD-induced colonic inflammation evidenced by the increased expression of proinflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) in the colon was also inhibited by β-sitosterol. In LPS-stimulated intestinal macrophages, β-sitosterol inhibited the production of proinflammatory cytokines and inflammatory enzymes as well as NF-κB activation. In addition, β-sitosterol significantly prevented the binding of LPS to intestinal as well as peritoneal macrophages. Furthermore, β-sitosterol potently inhibited the interaction between LPS and toll-like receptor 4 in intestinal macrophages transfected with control siRNA or MyD88 siRNA.

Conclusion

These findings indicate that β-sitosterol ameliorates HFD-induced colitis by inhibiting the binding of LPS to toll-like receptor 4 in the NF-κB pathway.

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