New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity
| Autor: | Nir Carmi, Zohar Kerem, Adi Nudel, Yuliya Zhmykhova, Iris Yedidia, Yelena Guttman |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
food.ingredient
Cytochrome Toxicology Grapefruit juice In silico docking 03 medical and health sciences chemistry.chemical_compound 0404 agricultural biotechnology food Cytochrome P-450 Enzyme System Furocoumarins Cytochrome P-450 Enzyme Inhibitors Cultivar 030304 developmental biology 0303 health sciences CYP3A4 biology Plant Extracts Chemistry food and beverages 04 agricultural and veterinary sciences General Medicine 040401 food science Bergamottin Kinetics Biochemistry Docking (molecular) Fruit biology.protein Drug metabolism Citrus paradisi Food Science |
| Zdroj: | Food and Chemical Toxicology. 137:111135 |
| ISSN: | 0278-6915 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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