Bakuchiol is a promising anti-
tumor candidate with
resveratrol-like structure. The present study aims to evaluate the inhibition potential of
bakuchiol towards
UDP-glucuronosyltransferases (UGT) 1A
isoforms. An in vitro incubation system using
4-methylumbelliferone (4-MU) glucuronidation was used to evaluate the inhibition capability of
bakuchiol towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The glucuronidation of
trifluoperazine (TFP) was employed as the probe reaction to determine
bakuchiol's inhibition towards UGT1A4. At 1 microM and 10 microM of
bakuchiol, no or weak inhibition was observed for all the tested UGT1A
isoforms. At 100 microM of
bakuchiol, the activity of UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9 and 1A10 was inhibited by -46.2%, 74.7%, 17.8%, 98.7%, 70.4%, 99.2%, 75.8%, and 93.3%, respectively. Further inhibition kinetic behaviour was determined for UGT1A6, 1A8, and 1A10. Both Dixon plot and Lineweaver-Burk plot showed the noncompetitive inhibition of
bakuchiol towards all these three UGT
isoforms. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 1.8, and 92.6 microM for UGT1A6, 1A8, and 1A10, respectively. In combination with the in vivo exposure of
bakuchiol, the high possibility of in vivo inhibition of UGT1A6 and 1A8 was predicted. However, relatively low possibility of in vivo inhibition towards
UGT1A10 was predicted due to lower in vivo concentration of
bakuchiol than its inhibition parameter (Ki). All these information will be helpful for the R&D of
bakuchiol as a promising anti-
tumor drug.