title: Radical scavenging and cytochrome P450 3A4 inhibitory activity of bergaptol and geranylcoumarin from grapefruit.
abstract: Grapefruit juice has been shown to increase the oral bioavailability of several clinically important drugs by inhibiting first pass metabolism. Several compounds in grapefruit juice have shown different biological activities. Unique among them are furocoumarins with potent inhibitory activity against cytochrome P450 enzymes. In the present study, two bioactive compounds were isolated from grapefruit juice and grapefruit peel oil. The purity of the isolated compounds has been analyzed by HPLC. Structures of the compounds were elucidated by extensive NMR and mass spectral studies and identified as bergaptol and geranylcoumarin. The isolated compounds were tested for their radical scavenging activity using 2,2'-azobis (3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazil (DPPH) methods at different concentrations. Bergaptol showed very good radical scavenging activity at all the tested concentrations. Furthermore, these compounds were evaluated for their inhibitory activity against CYP3A4 enzyme. Bergaptol and geranylcoumarin were found to be potent inhibitors of debenzylation activity of CYP3A4 enzyme with an IC(50) value of 24.92 and 42.93 microM, respectively.
authors.affiliation: Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, 2119, Texas A&M University, College Station, TX 77843-2119, USA.
authors.forename: Basavaraj
authors.initials: B
authors.lastname: Girennavar
authors.forename: G K
authors.initials: GK
authors.lastname: Jayaprakasha
authors.forename: Y
authors.initials: Y
authors.lastname: Jadegoud
authors.forename: G A
authors.initials: GA
authors.lastname: Nagana Gowda
authors.forename: Bhimanagouda S
authors.initials: BS
authors.lastname: Patil
mesh_terms: D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry*; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology*; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans
chemical_list: D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004224:Diterpenes; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D011564:Furocoumarins; C521390:geranylcoumarin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C080771:bergaptol