Biotransformation of Polymethoxyflavones by Mouse and Human Colonic Microflora

Colonic microflora plays important roles in biotransformation of dietary components and their biological activities. Polymethoxyflavones (PMFs), a unique class of flavonoids found in citrus fruits have shown many beneficial bioactivities. We investigated the biotransformation of two representative PMFs i.e. nobiletin (NBT) and 5‐hydroxylnobiletin (5HN) by colonic microflora. NBT, 5HN and their metabolites were isolated from the urine of CD‐1 mice after oral administration of NBT or 5HN for 2 weeks. These isolates were subject to anaerobic fermentation by colonic microflora freshly isolated from CD‐1 mice and human volunteers. HPLC analysis demonstrated that colonic microflora had no effect on NBT or 5HN. However, glucuronide and sulfate conjugates of NBT and 5HN metabolites were largely deconjugated by colonic microflora. Colonic microflora also caused demethylation at certain positions of flavonoid core structures, e.g. 3′ and 4′ positions on B‐ring. Both mouse and human colonic microflora produced similar effects on PMFs. Moreover, our results in cell culture models demonstrated that isolates generated after colonic microflora fermentation showed much stronger anti‐inflammatory and anti‐carcinogenic effects than isolates without fermentation. Overall, we provided the first report on the biotransformation of PMFs by colonic microflora and its potential for enhancing health benefits of PMFs. Grant Funding Source : AICR, NIH, NAS and USDA