Inhibitory activity of diacylglycerol acyltransferase by glabrol isolated from the roots of licorice

Acyl-coenzyme A: diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes triglyceride synthesis in the glycerol phosphate pathway. It has relations with the excess supply and accumulation of triglycerides. Therefore, DGAT inhibitors may act as a potential therapy for obesity and type 2 diabetes. Five flavonoids were isolated from the ethanol extracts of licorice roots, using an in vitro DGAT inhibitory assay. One isoprenyl flavonoid showed most potential inhibition of DGAT on five flavonoids ( 1 – 5 ). On the basis of spectral evidences, the compound was identified as glabrol ( 5 ). Compound 5 inhibited rat liver microsomal DGAT activity with an IC50 value of 8.0 µM, but the IC50 value for four flavonoids ( 1 – 4 ) was more than 100 µM. In addition, glabrol showed a noncompetitive type of inhibition against DGAT. These data suggest that potential therapy for the treatment in obesity and type 2 diabetes patients by licorice roots might be related with its DGAT inhibitory effect.