Natural CAC chemopreventive agents from Ilex rotunda Thunb.
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.
KeywordsColitis-associated cancer Ilex rotunda Thunb. Inflammatory bowel disease Active ingredients Rotundic acid
The work was supported partially by the National Natural Science Foundation of China (Grant nos. 81673323, 81872768, 81628012); the Open Research Funding of Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use (2018KF05); and the young and middle-aged teachers’ career development support plan of Shenyang Pharmaceutical University (ZCQ201701).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no disclosures to report.
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