Binding of furanocoumarins in grapefruit juice to Aspergillus niger hyphae.

Furanocoumarins (FCs) in grapefruit are involved in the "grapefruit/drug interactions" in humans, in which the FCs inhibit the intestinal cytochrome P450 3A4 (CYP 3A4) activity responsible for metabolizing certain prescribed medications. These interactions have adversely affected the grapefruit industry and have led a need to develop a process to remove the FCs from grapefruit juice (GFJ) in a manner that retains much of the original juice sensory attributes. In our experiments, grapefruit juice was incubated with Aspergillus niger, and the compositional changes in hydroxycinnamates, flavonoid glycosides, and the FCs were monitored. Many of the FCs and 7-geranyloxycoumarin were efficiently taken up by the fungal tissue, whereas no uptake occurred with the polar hydroxycinnamates, flavonoid glycosides, and a few of the polar FCs. This biosorption was also observed with autoclaved A. niger, indicating that the uptake of non-polar FCs by the fungal hyphae was due to adsorption rather than metabolism. The binding of the FCs to autoclaved fungus was complete within 4 h, and the level of binding was proportional to the amount of autoclaved fungal hyphae used. This removal of the FCs from GFJ led to a reduced inhibition of CYP 3A4 activity in in vitro assays by both GFJ and GFJ extracts.