Psoralen, a mechanism-based inactivator of CYP2B6

被引：27

作者：

Ji, Lin ^{[1
]}

Lu, Dan ^{[1
]}

Cao, Jiaojiao ^{[1
]}

Zheng, Liwei ^{[1
]}

Peng, Ying ^{[1
]}

Zheng, Jiang ^{[2
,3
]}

机构：

[1] Shenyang Pharmaceut Univ, Coll Pharm, Shenyang 110016, Liaoning, Peoples R China

[2] Shenyang Pharmaceut Univ, Minist Educ, Key Lab Struct Based Drug Design & Discovery, Shenyang 110016, Liaoning, Peoples R China

[3] Univ Washington, Ctr Dev Therapeut, Seattle Childrens Res Inst, Div Gastroenterol & Hepatol,Dept Pediat,Sch Med, Seattle, WA 98101 USA

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2015年 / 240卷

基金：

中国国家自然科学基金;

关键词：

Psoralen; Cytochrome P450 2B6; Mechanism-based inactivation; Reactive metabolite; CYTOCHROME P4502B6; IN-VITRO; INHIBITION; METABOLISM; BERGAMOTTIN; BAKUCHIOL; THERAPY; MARKER; 1A2; 3A4;

D O I：

10.1016/j.cbi.2015.08.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Furanocoumarin compound psoralen (PRN) is a major active ingredient found in herbaceous plants. PRN has been used for the treatment of various dermal diseases in China. We evaluated the inhibitory effect of PRN on cytochrome P450 2B6 (CYP2B6) and found that PRN induced a time-, concentration-, and NADPH-dependent inactivation of CYP2B6 with the values of K-I and k(inact) being 110.2 mu M and 0.200 min(-1), respectively. Ticlopidine, a CYP2B6 substrate, prevented the enzyme from the inactivation induced by PRN. Exogenous nucleophile glutathione (GSH) and catalase/superoxide dismutase showed limited protection of CYP2B6 from the inactivation. The estimated partition ratio of the inactivation was approximately 400. GSH trapping experiments indicates that an epoxide or/and gamma-ketoenal intermediate was formed in microsomal incubations with PRN. In summary, PRN was characterized as a mechanism-based inactivator of CYP2B6. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

引用

页码：346 / 352

页数：7

共 31 条

[1]

Backhouse CN, 2001, J ETHNOPHARMACOL, V78, P27, DOI 10.1016/S0378-8741(01)00309-9

[2] INHIBITION AND INACTIVATION OF MURINE HEPATIC ETHOXYRESORUFIN AND PENTOXYRESORUFIN O-DEALKYLASE BY NATURALLY-OCCURRING COUMARINS [J].

CAI, YN ;

BENNETT, D ;

NAIR, RV ;

CESKA, O ;

ASHWOODSMITH, MJ ;

DIGIOVANNI, J .

CHEMICAL RESEARCH IN TOXICOLOGY, 1993, 6 (06) :872-879

[3] Mechanism-based inactivation of cytochrome P450 2B6 by isoimperatorin [J].

Cao, Jiaojiao ;

Zheng, Liwei ;

Ji, Lin ;

Lu, Dan ;

Peng, Ying ;

Zheng, Jiang .

CHEMICO-BIOLOGICAL INTERACTIONS, 2015, 226 :23-29

[4]

Chen Hong-li, 2010, Yaoxue Xuebao, V45, P467

[5]

Faucette SR, 2000, DRUG METAB DISPOS, V28, P1222

[6] Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19 [J].

Gerber, JG ;

Rhodes, RJ ;

Gal, J .

CHIRALITY, 2004, 16 (01) :36-44

[7] Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice [J].

He, K ;

Iyer, KR ;

Hayes, RN ;

Sinz, MW ;

Woolf, TF ;

Hollenberg, PF .

CHEMICAL RESEARCH IN TOXICOLOGY, 1998, 11 (04) :252-259

[8]

Huang Z., 2000, BIOCHEM PHARMACOL, V159, P961

[9] Effects of Furanocoumarins from Apiaceous Vegetables on the Catalytic Activity of Recombinant Human Cytochrome P-450 1A2 [J].

Kang, Ah-Young ;

Young, Lindsay R. ;

Dingfelder, Carlus ;

Peterson, Sabrina .

PROTEIN JOURNAL, 2011, 30 (07) :447-456

[10] In vitro antimicrobial activities of bakuchiol against oral microorganisms [J].

Katsura, H ;

Tsukiyama, RI ;

Suzuki, A ;

Kobayashi, M .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (11) :3009-3013

← 1 2 3 4 →