Identification of novel bioactive metabolites of 5‐demethylnobiletin in mice. Issue 11 (26th July 2013)

• Record Type: Journal Article
• Authors: Zheng, Jinkai; Song, Mingyue; Dong, Ping; Qiu, Peiju; Guo, Shanshan; Zhong, Zhimei; Li, Shiming; Ho, Chi‐Tang; Xiao, Hang
• Is Part Of: Molecular nutrition & food research. Volume 57:Issue 11(2013:Nov.)
• Page Start: 1999
• Page End: 2007
• Publication Date: 2013-07-26
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201300211
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr2024-sec-0010" sec-type="section"> <title>Scope</title> <p>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.</p> </sec> <sec id="mnfr2024-sec-0020" sec-type="section"> <title>Methods and results</title> <p>Urine samples were collected from mice fed with 5‐demethylnobiletin (<bold>1</bold>) and analyzed by LC‐ESI‐MS and HPLC coupled with an electrochemical detector. Three major metabolites were identified as 5, 3′‐didemethylnobiletin (<bold>2</bold>), 5, 4′‐didemethylnobiletin (<bold>3</bold>), and 5, 3′, 4′‐tridemethylnobiletin (<bold>4</bold>) 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 (<bold>2</bold>), showed much stronger inhibitory effects on cancer cell growth than 5‐demethylnobiletin. For example, metabolites (<bold>2</bold>–<bold>4</bold>) showed IC<sub>50</sub> 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.</p> </sec> <sec id="mnfr2024-sec-0030" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>