TY - JOUR T1 - Natural naphthoquinones isolated from <em>Lithospermum erythrorhizon</em> suppress dextran sulfate sodium-induced murine experimental colitis JF - bioRxiv DO - 10.1101/830224 SP - 830224 AU - Wenxue Sun AU - Hongwei Han AU - Zhaoyue Wang AU - Zhongling Wen AU - Minkai Yang AU - Yinsong Wang AU - Jiangyan Fu AU - Lu Feng AU - Xinhong Xu AU - Tongming Yin AU - Xiaoming Wang AU - Guihua Lu AU - Jinliang Qi AU - Hongyan Lin AU - Yonghua Yang Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/04/830224.abstract N2 - The purpose of this study was to explore the effects of natural shikonin and its derivatives on mice experimental colitis induced by dextran sulfate sodium, and to investigate the underlying mechanisms in vivo. Our results suggested that, intragastric administration of single compound like shikonin and its derivatives contributed to attenuating symptoms of malignant induced by DSS. Meanwhile, shikonin or its derivatives could also remarkably reduce the disease activity index and histopathological scores, suppress the levels of pro-inflammatory cytokines (including IL-6, IL-1β and TNF-α), while increase that of inflammatory cytokine IL-10 in serum. Additionally, both shikonin and alkanin were found to restrain the levels of COX-2, MPO and iNOS in serum and colonic tissues. Moreover, western blotting results demonstrated that shikonin and its derivatives could inhibit the activation of the NLRP3 inflammasome and the NF-κB signaling pathway, relieve the DSS-induced disruption of colonic epithelial tight junction (TJ) in colonic tissues. Further, docking simulation had been performed to prove that shikonin and its derivatives could bind to the active sites of NLRP3 inflammasome and the NF-κB to generate an effective inflammatory effect. Taken together, our experimental data can provide some evidence for the potential use of shikonin and its derivatives to treat the inflammatory bowel disease (IBD).AbbreviationsDSSdextran sulfate sodiumIL-1βinterleukin1βIL-6interleukin6TNF-αtumor necrosis factor-αIL-10interleukin10COX-2cyclooxygenase-2MPOmyeloperoxidaseiNOSinducible nitric oxide synthaseASCapoptosis-associated speck-like protein containing CARDNLRP3nod-like receptor protein3NF-κBnuclear factor-kappa BTJtight junctionIBDinflammatory bowel diseaseCRCcolorectal cancerTCMtraditional Chinese medicineSKshikoninAKalkaninacetyl-SKacetyl-shikoninββ-dimethylacryl-SK, β-dimethylacryl-shikoninDAIdisease activity indexHEhaematoxylin &amp; EosinRIPAradio immunoprecipitation assayPVDFpolyvinylidene fluorideHRPhorseradish peroxidaseUCulcerative colitisZO-1zonula occludensVCAM-1vascular cell adhesion protein 1HMhydroxynaphthoquinone mixtureTNBS2, 4, 6-tri-nitrobenzene sulfonic acid ER -