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Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation

Oroxyloside prevents dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-κB pathway through PPARγ activation

Biochemical pharmacology 106: 70-81

ISSN/ISBN: 1873-2968

PMID: 26947454

DOI: 10.1016/j.bcp.2016.02.019

Oroxyloside, as a metabolite of oroxylin A, may harbor various beneficial bioactivities which have rarely been reported in the previous studies. Here we established the dextran sulfate sodium (DSS)-induced experimental colitis and evaluated the anti-inflammatory effect of oroxyloside in vivo. As a result, oroxyloside attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. Furthermore, oroxyloside inhibited inflammatory cell infiltration and decreased myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities as well. The production of pro-inflammatory cytokines in serum and colon was also significantly reduced by oroxyloside. We unraveled the underlying mechanisms that oroxyloside inhibited NF-κB pathway by activating Peroxisome Proliferator-Activated Receptor γ (PPARγ) to attenuate DSS-induced colitis. Moreover, we investigated the anti-inflammatory effect and mechanisms of oroxyloside in the mouse macrophage cell line RAW264.7 and bone marrow derived macrophages (BMDM). Oroxyloside decreased several LPS-induced inflammatory cytokines, including IL-1β, IL-6 and TNF-α in RAW264.7 and BMDM. We also found that oroxyloside inhibited LPS-induced activation of NF-κB signaling pathway via activating PPARγ in RAW 264.7 and BMDM. Docking study showed that oroxyloside could bind with PPARγ. GW9662, the inhibitor of PPARγ, and PPARγ siRNA transfection blocked the effect of oroxyloside on PPARγ activation. Our study suggested that oroxyloside prevented DSS-induced colitis by inhibiting NF-κB pathway through PPARγ activation. Therefore, oroxyloside may be a promising and effective agent for inflammatory bowel disease (IBD).

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