New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity.

Food Chem Toxicol

Institute of Plant Sciences, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel. Electronic address:

Published: March 2020

Furanocoumarins are the main compounds responsible for the food-drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6',7'-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food-drug interactions.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2020.111135DOI Listing

Publication Analysis

Top Keywords

grapefruit cultivars
8
food-drug interactions
8
cyp3a4 activity
8
juice compounds
8
grapefruit
7
cyp3a4
5
cultivars exhibit
4
exhibit low
4
low cytochrome
4
cytochrome p4503a4-inhibition
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!