Radical scavenging and cytochrome P450 3A4 inhibitory activity of bergaptol and geranylcoumarin from grapefruit

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 IC50 value of 24.92 and 42.93 μM, respectively.

Bergaptol and geranylcoumarin were isolated from grapefruit and characterized using MS and NMR studies. Both the compounds were tested for their radical scavenging property using ABTS and DPPH methods. Bergaptol showed very good antioxidant potential and geranylcoumarin showed least activity. Further, these compounds were evaluated for cytochrome P450 CYP3A4 inhibition potential. Bergaptol and geranylcoumarin found to be potent inhibition of debenzylation activity of CYP3A4 enzyme with IC50 value of 24.92 and 42.93 μM, respectively.Figure optionsDownload as PowerPoint slide