|
KMID : 0606920140220020155
|
|
Biomolecules & Therapeutics
2014 Volume.22 No. 2 p.155 ~ p.160
|
|
|
A Comparison of the In Vitro Inhibitory Effects of Thelephoric Acid and SKF-525A on Human Cytochrome P450 Activity
|
|
Song Min
Do Hyun-Hee
Kwon Oh-Kwang
Yang Eun-Ju
Bae Jong-Sup
Jeong Tae-Cheon
Song Kyung-Sik
Lee Sang-Kyu
|
|
|
Abstract
|
|
|
|
Thelephoric acid is an antioxidant produced by the hydrolysis of polyozellin, which is isolated from Polyozellus multiplex. In the present study, the inhibitory effects of polyozellin and thelephoric acid on 9 cytochrome P450 (CYP) family members (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) were examined in pooled human liver microsomes (HLMs) using a cocktail probe assay. Polyozellin exhibited weak inhibitory effects on the activities of all 9 CYPs examined, whereas thelephoric acid exhibited dose- and time-dependent inhibition of all 9 CYP isoforms (IC50 values, 3.2?33.7 μM). Dixon plots of CYP inhibition indicated that thelephoric acid was a competitive inhibitor of CYP1A2 and CYP3A4. In contrast, thelephoric acid was a noncompetitive inhibitor of CYP2D6. Our findings indicate that thelephoric acid may be a novel, non-specific CYP inhibitor, suggesting that it could replace SKF-525A in inhibitory studies designed to investigate the effects of CYP enzymes on the metabolism of given compounds.
|
|
|
KEYWORD
|
|
|
Thelephoric acid, Polyozellin, SKF-525A, Cytochrome P450, Non-specific inhibitor
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|