Minor Furanocoumarins and Coumarins in Grapefruit Peel Oil as Inhibitors of Human Cytochrome P450 3A4

Abstract

A new cyclic acetal (1) of marmin (6',7'-dihydroxy-7-geranyloxycoumarin), two new cyclic acetals (5, 6) of 6',7'-dihydroxybergamottin, and the known compounds marmin (2), 7-geranyloxycoumarin (3), bergamottin (4), and 6',7'-dihydroxybergamottin (7) were isolated from grapefruit peel oil. All compounds were tested for inhibitory activity against intestinal cytochrome P450 3A4, an enzyme involved in the "grapefruit/drug" interactions in humans. Coumarins (1-3) exhibited negligible inhibitory activity, while the furanocoumarins (4-7) showed potent in vitro inhibitory activity with IC(50) values of 2.42, 0.13, 0.27, and 1.58 microM, respectively.

Chemical Composition, Antimicrobial, Antioxidant, and Antiproliferative Properties of Grapefruit Essential Oil Prepared by Molecular Distillation

“…Large scale production, low cost and the aroma characteristic remaining are the big advantages of the cold-pressing method. However, cold-pressed grapefruit oil contains waxes, pesticide residues, coumarins, carotenoids and other nonvolatile components [28][29][30], some of them also have good bioactivities that may cause bias in bioactivity research of EO. César et al (2009) found that furanocoumarins isolated from grapefruit peel oil showed potent in vitro inhibitory activity against intestinal cytochrome P450 3A4, an enzyme involved in "grapefruit/drug" interactions in humans [28].…”

“…However, cold-pressed grapefruit oil contains waxes, pesticide residues, coumarins, carotenoids and other nonvolatile components [28][29][30], some of them also have good bioactivities that may cause bias in bioactivity research of EO. César et al (2009) found that furanocoumarins isolated from grapefruit peel oil showed potent in vitro inhibitory activity against intestinal cytochrome P450 3A4, an enzyme involved in "grapefruit/drug" interactions in humans [28]. Steam distillation or hydrodistillation was carried out at relatively high temperature which may cause degradation of some thermal sensitive molecules [18,31].…”

Protein Sequestration of Lipophilic Furanocoumarins in Grapefruit Juice

“…BM, 6′,7′epoxybergamottin, and DHB were isolated as reported previously. 14 Bergapten (5-methoxypsoralen) (product number 27,572-7) was purchased from Aldrich Chemical Co.…”

“…The Bradford protein assay was run with a BSA protein standard ampule from Thermo Scientific. BM, 6′,7′-epoxybergamottin, and DHB were isolated as reported previously . Bergapten (5-methoxypsoralen) (product number 27,572-7) was purchased from Aldrich Chemical Co.…”

Human Cytochrome P450 Liability Studies of trans-Dihydronarciclasine: A Readily Available, Potent, and Selective Cancer Cell Growth Inhibitor

“…The CYP3A subfamily comprises about 30% of the total liver cytochrome P450 enzyme pool in humans, and the isoenzyme CYP3A4 accounts for approximately 60% of drugs metabolized . Many drug development programs have failed or are dose-compromised due to interactions with this most predominant enzyme . Inhibition of CYP3A4 can lead to drug accumulation, contribute significantly to negative drug−drug interactions, and may lead to hepatic toxicity.…”