Inhibitory effect of cannabidiol hydroxy-quinone, an oxidative product of cannabidiol, on the hepatic microsomal drug-metabolizing enzymes of mice.
Cannabidiol hydroxy-quinone (CBDHQ) was identified as an air oxidation product of cannabidiol (CBD). The in vitro incubation of mouse hepatic microsomes with CBDHQ resulted in a decrease of cytochrome P-450 content. CBDHQ inhibited the hepatic microsomal drug-metabolizing enzymes of mice. This inhibitory effect was stronger than that of CBD. CBDHQ (150 microM) inhibited aniline hydroxylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase in the microsomes by 70, 52 and 77%, respectively, whereas the same concentration of CBD caused the inhibition by 39, 30 and 26%, respectively. CBDHQ (91.5 microM) significantly decreased total heme content by 21% and free SH groups by 11% in the microsomes. The results indicate that CBDHQ, which is an oxidation product of CBD, inhibits the hepatic microsomal drug-metabolizing enzymes through the decrease of cytochrome P-450 content.
Watanabe
K
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Usami
N
N
Yamamoto
I
I
Yoshimura
H
H
D000818:Animals; D002185:Cannabidiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction
C073718:cannabidiol hydroxyquinone; D002185:Cannabidiol