Document Detail

Reversible inhibition of three important human liver cytochrome p450 enzymes by tiliroside.
MedLine Citation:
PMID:  21031626     Owner:  NLM     Status:  MEDLINE    
Tiliroside, an active flavonoid extensively found in many medicinal plants including Helichrysum italicum, Geranium mexicanum and Helianthemum glomeratum, has been demonstrated to exert multiple biological effects including antiinflammatory, antimicrobial, antioxidant and antitumor activities. Cytochrome P450 (CYP) enzymes play an important role in the Phase I oxidation metabolism of a wide range of xenobiotics and inhibition of CYP isoforms might influence the elimination of drugs and induce serious adverse drug response. The inhibition of seven CYP isoforms (CYP3A4, CYP1A2, CYP2A6, CYP2D6, CYP2C9, CYP2C8 and CYP2E1) by tiliroside was investigated using in vitro human liver microsomal incubation assays. The results showed that tiliroside strongly inhibited the activity of CYP3A4 (IC(50) = 9.0 ± 1.7 μm), CYP2C8 (IC(50) = 12.1 ± 0.9 μm) and CYP2C9 (IC(50) = 10.2 ± 0.9 μm) with other CYP isoforms negligibly influenced. Further kinetic analysis showed that inhibition of these three CYP isoforms by tiliroside is best fit to a competitive way. The K(i) value was calculated to be 5.5 μm, 3.3 μm, 9.4 μm for CYP3A4, CYP2C9 and CYP2C8, respectively. The relatively low K(i) values suggested that tiliroside might induce drug-drug interactions with many clinically used drugs which are mainly metabolized by these three CYP isoforms. Therefore, attention should be given to the probable drug-drug interaction between tiliroside-containing herbs and substrates of CYP3A4, CYP2C9 and CYP2C8.
Dong-Xue Sun; Jin-Cai Lu; Zhong-Ze Fang; Yan-Yan Zhang; Yun-Feng Cao; Yu-Xi Mao; Liang-Liang Zhu; Jun Yin; Ling Yang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Phytotherapy research : PTR     Volume:  24     ISSN:  1099-1573     ISO Abbreviation:  Phytother Res     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8904486     Medline TA:  Phytother Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1670-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 John Wiley & Sons, Ltd.
School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, 110016, China.
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MeSH Terms
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
Cytochrome P-450 CYP3A / antagonists & inhibitors*
Flavonoids / pharmacology*
Microsomes, Liver / drug effects
Reg. No./Substance:
0/Flavonoids; 20316-62-5/tiliroside; EC protein, human; EC Hydrocarbon Hydroxylases; EC protein, human; EC protein, human; EC P-450 CYP3A

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