Natural CAC chemopreventive agents from Ilex rotunda Thunb.

  • Yueqing Han
  • Lin Zhang
  • Wei Li
  • Xinran Liu
  • Jiao Xiao
  • Gang ChenEmail author
  • Ning LiEmail author
Original Paper


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.


Colitis-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.

Supplementary material

11418_2019_1281_MOESM1_ESM.docx (373 kb)
Supplementary material 1 (DOCX 373 kb)


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Copyright information

© The Japanese Society of Pharmacognosy 2019

Authors and Affiliations

  1. 1.Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research and DevelopmentSchool of Traditional Chinese Materia Medica, Shenyang Pharmaceutical UniversityShenyangChina
  2. 2.Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
  3. 3.Faculty of Pharmaceutical SciencesToho UniversityFunabashiJapan

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