ARS | Publication request: In vitro inhibition of CYP3A4 activity by some newly-isolated minor-occurring furanocoumarins in grapefruit juice

Submitted to: Subtropical Technology Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: September 11, 2006
Publication Date: October 18, 2006
Citation: Myung, K., Manthey, J.A. 2006. In vitro inhibition of CYP3A4 activity by some newly-isolated minor-occurring furanocoumarins in grapefruit juice. Subtropical Technology Conference Proceedings. 57:18-19.

Technical Abstract: A number of furanocoumarins, which are minor phenolic constituents in plants, have been extensively studied for their biological functions in plant defense mechanisms, grapefruit-drug interactions, and therapeutic medications. In grapefruit-drug interactions, it has been shown that furanocoumarins act as natural inhibitors of cytochrome P450 (CYP) enzymes, thus interfering with the metabolism of a variety of substrates. The mass spectra shows eleven newly-isolated minor-occurring furanocoumarins in grapefruit juice. These furanocoumarins were tested for their inhibition of in vitro CYP3A4 activity and compared to those of known furanocoumarin standards, such as bergamottin, 6', 7'-dihydroxybergamottin, and 6', 7'-epoxybergamottin. Three unknown compounds showed IC50 values similar to the known standards. Two furanocoumarin dimers exhibited the lowest IC50 values of 2.16 and 1.68 ng •100 mL-1, respectively. In addition, IC50 values of four other unknown compounds were significantly lower than those of bergamottin, 6', 7'-dihydroxybergamottin, and 6', 7'-epoxybergamottin. In contrast, the IC50 values of two compounds were higher than those of the standards. Our results support the known relationship between chemical structure and inhibition of CYP3A4 activity. Furthermore, these results suggest that minor-occurring furanocoumarins are potent inhibitors of CYP3A4, and play important roles in grapefruit-drug interactions.