Identification of novel bioactive metabolites of 5-demethylnobiletin in mice

Jinkai Zheng, Mingyue Song, Ping Dong, Peiju Qiu, Shanshan Guo, Zhimei Zhong, Shiming Li, Chi Tang Ho, Hang Xiao

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Scope: Biotransformation of dietary components is important for their in vivo biological activities after oral ingestion. Herein, we investigated biotransformation of 5-demethylnobiletin (a polymethoxyflavone found in citrus fruits) in mice, and its implication in the inhibition of human colon cancer cells. Methods and results: Urine samples were collected from mice fed with 5-demethylnobiletin (1) and analyzed by LC-ESI-MS and HPLC coupled with an electrochemical detector. Three major metabolites were identified as 5,3′-didemethylnobiletin (2), 5,4′-didemethylnobiletin (3), and 5,3′,4′-tridemethylnobiletin (4) by comparing their ESI-MS and HPLC profiles with those of authentic standards synthesized by a multistep route. Cell viability assay in human colon cancer cells demonstrated that all three metabolites of 5-demethylnobiletin, especially 5,3′-didemethylnobiletin (2), showed much stronger inhibitory effects on cancer cell growth than 5-demethylnobiletin. For example, metabolites (2-4) showed IC50 of 0.12, 5.5, and 4.2 μM in SW620 cells, respectively, while 5-demethylnobiletin at 10 μM only caused 37% inhibition after 72 h of treatment. Conclusion: Three novel metabolites were identified in mice after oral administration of 5-demethylniobiletin. These metabolites exhibited strong inhibitory effects against human colon cancer cells. Our results provide a first report on these bioactive metabolites and warrant further investigation on their molecular mechanism of actions.

Original languageEnglish (US)
Pages (from-to)1999-2007
Number of pages9
JournalMolecular Nutrition and Food Research
Issue number11
StatePublished - Nov 2013

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Food Science


  • 5,3′-Didemethylnobiletin
  • 5-Demethylnobiletin
  • Cancer inhibition
  • Metabolites

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