Inhibitory activity of sesaminol and sesaminol triglycoside on cytochrome P450 enzymes and their pharmacokinetics in rats

Sesame lignans have been shown to possess several health benefits. Lignans with a methylenedioxyphenyl group such as sesaminol, sesaminol triglycoside, sesamin or sesamolin are major constituents of sesame. Bioavailability of plant lignans is affected by phytochemical structure and metabolized enzyme (cytochrome P450, CYP). This investigation studied the interference of CYPs on bioavailability of sesaminol and sesaminol triglycoside. Biological fluids were sampled following orally fed sesaminol (120 mg/kg) and sesaminol triglycoside (100 mg/kg), and intravenously injected sesaminol (30 mg/kg) and sesaminol triglycoside (100 mg/kg) through the femoral vein. Results show that maximum concentrations were 0.2 ± 0.1 and 0.7 ± 0.2 μg/mL, and the area under the concentration-time curve were 17.2 ± 2.8 and 17.6 ± 7.6 min μg/mL after a single oral ingestion of sesaminol triglycoside and sesaminol, respectively. The clearances were 16.4 ± 6.57 and 396 ± 53.6 mL/min kg, and half-lives were 50.0 ± 13.3 and 74.0 ± 28.4 min via intravenous injection of sesaminol triglycoside and sesaminol, respectively. Our results show that the oral bioavailability of sesaminol and sesaminol triglycoside was 21.0 ± 8.6% and 0.3 ± 0.1%, respectively. This study also demonstrates that sesaminol has a more potent inhibitory activity of CYPs, compared to sesaminol triglycoside. The IC50 values of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 for sesaminol were determined as 0.88, 0.94, 0.78, 4.04 and 0.68 μM, respectively.