P108 Selective inhibitory effect of Fisetin and Geraldol, its methylated metabolite, in Human Liver Microsome

Woongshik Nam , Kyungpook National University, Daegu, Korea, The Republic of
Selective inhibitory effect of Fisetin and Geraldol, its methylated metabolite, in Human Liver Microsome

Woongshik Nam, Sangkyu Lee

BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea

Fisetin is a Flavonol compound that is contained in edible vegetables and fruits that are commonly found, such as strawberry, apple and onion, and has anti-tumor, anti-oxidant and anti-inflammatory effects.  Geraldol is a metabolite that is methoxylated when Fisetin is injected into the body, and is reported to suppress endothelial cell migration and proliferation.  Whereas the in vivo and in vitro effects of Fisetin are frequently reported, studies on herb-drug interaction haven’t been conducted yet.  This study conducted CYP inhibition assessment on Fisetin and Geraldol to estimate their interaction with other herbal extractions or drugs.

Selective inhibition of Fisetin and its metabolite, Geraldol, against CYP 2C8 was confirmed through CYP inhibition assay.  Through additional IC50 shift assay, it was confirmed that the two compounds displayed No time-dependent inhibitions; through Lineweaver-burke plot, it was also confirmed that they showed Non-competitive inhibition mode.  Also, through the Ki value obtained from plotted graph, Geraldol was confirmed to have stronger inhibition against CYP 2C8 than Fisetin.

The CYP inhibition assessment of Fisetin and Geraldol will hold significance as an initial experiment in herb-drug interaction between Fisetin, its metabolome Geraldol, and other drugs.