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13.02.2019 | Original Paper | Ausgabe 3/2019

Journal of Natural Medicines 3/2019

Natural CAC chemopreventive agents from Ilex rotunda Thunb.

Journal of Natural Medicines > Ausgabe 3/2019
Yueqing Han, Lin Zhang, Wei Li, Xinran Liu, Jiao Xiao, Gang Chen, Ning Li
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Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s11418-019-01281-z) contains supplementary material, which is available to authorized users.
Yueqing Han and Lin Zhang have contributed equally to this article.

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Colitis-associated cancer (CAC) is one of the most serious complications of inflammatory bowel disease. The pathogenesis of CAC is complicated and so far elusive, and the anti-inflammatory effect does not assure CAC preventive activity, making it difficult to discover CAC preventive drugs. In this study, we report the CAC preventive effect of the ethyl acetate (EIR) of Ilex rotunda Thunb., a traditional Chinese herbal medicine being clinically used to treat intestinal disease. We also report the results of screening for CAC preventive agents from EIR via a nuclear factor-kappa B (NF-κB) translocation model in Caco2 cells, since activated NF-κB can be used by tumor cells at the early stage of tumorigenesis. Twenty-four components were isolated from EIR and identified by multiple chromatography and spectral analysis. MTT experiments in IEC-6 and RAW264.7 cells showed that all 24 compounds were toxic-free to normal cell lines. Furthermore, compound rotundic acid (RA) (19) exhibited an inhibitory effect on LPS-induced NF-κB translocation in Caco2 cells. Moreover, RA did not induce apoptosis in Caco2 tumor cells while possessing an anti-inflammatory effect both in immune and intestinal epithelium cells (RAW264.7 and IEC-6 cells, respectively). Removing RA (19) and its 28-O-glucopyranoside (17) from EIR definitely undermined the in vivo CAC preventive activity of EIR. Therefore, the current study suggested that RA (19) could be a potential therapeutic agent against CAC.

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