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Biotransformation of citrus polymethoxyflavones in rats and mice (1044.22)
Author(s) -
Zheng Jinkai,
Song Minyue,
Qiu Peiju,
Dong Ping,
Cai Xiaokun,
Xiao Hang
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1044.22
Subject(s) - biotransformation , urine , feces , chemistry , demethylation , nobiletin , metabolite , high performance liquid chromatography , chromatography , food science , metabolomics , pharmacology , biochemistry , biology , flavonoid , microbiology and biotechnology , enzyme , gene expression , antioxidant , gene , dna methylation
Biotransformation plays important roles in dictating biological activities of orally ingested agents including all bioactive food compounds. We investigated biotransformation of four representative citrus polymethoxyflavones (PMFs), i.e. nobiletin, tangeretin, 5‐demethylnobiletin and 5‐demethyltangeretin in both rats and mice after long‐term oral consumption. Four PMFs were administered individually to rats and mice through diet at different doses for 10‐20 weeks. Their feces and urine were collected in metabolic cages. Utilizing NMR, MS and HPLC techniques, we identified more than 20 metabolites of these PMFs in the fecal and urine samples. We optimized the extraction and HPLC analysis conditions so that we can simultaneously quantify all PMFs and their metabolites in a single HPLC run with high sensitivity. Our results showed that all four PMFs underwent extensive demethylation reaction followed by conjugation reactions (mainly sulfation and glucuronidatioin). However, the ratios between conjugated and unconjugated metabolites in the feces and urine are largely different. Cell culture studies demonstrated that metabolites in feces had much stronger anti‐cancer and anti‐inflammatory effects in comparison with those from urine, which was contributed to certain unconjugated fecal metabolites. Our results warrant further investigation on the effects of fecal metabolites on colon health. Grant Funding Source : Supported by NIH, AICR and USDA