title: Inhibitory effect of Aristolochia fruit on Cytochrome P450 isozymes in vitro and in vivo.
abstract: The mature fruits of Aristolochia debilis, known in China by the name, "Madouling" has been popularly prescribed in Asia, particularly in China, to treat a range of conditions including gynaecological problems, arthritis and wound healing. This study was aimed to evaluate the potential effect of Madouling on the cytochrome P450 (CYP) isozymes in vitro in microsomal fractions and in vivo in rats. The influence of Madouling on CYPs activity was first explored by an in vitro method of estimating levels of four respective metabolites in rat liver microsomes. The results were re-examined in vivo in rats by using a cocktail approach involving the probe drugs theophylline, tolbutamide, chlorzoxazone and dapsone. Pharmacokinetics of the four substrates was used to analyze the activities of the targeting isozymes. In vitro study revealed that Madouling decreased the activity of CYP1A2, 3A1 and 2E1. However, no significant influence on CYP2C6 was found. These results coincided with those of in vivo study to a great degree except that in vivo estimation the herb didn't inhibit CYP1A2 significantly. From the data obtained, Madouling is suggested as a candidate for clinically signiﬁcant CYP interactions. Drug co-administrated with Madouling may need dose adjustment.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China / The Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Gao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Faculty of Pharmacy, University of Sydney, NSW, Australia.
authors.forename: George
authors.initials: G
authors.lastname: QLi
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zuanguang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Meicun
authors.initials: M
authors.lastname: Yao
mesh_terms: D000818:Animals; D030022:Aristolochia; D019388:Cytochrome P-450 CYP1A2; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D000072467:Cytochrome P450 Family 2; D003580:Cytochromes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057075:Enzyme Assays; D005638:Fruit; D066298:In Vitro Techniques; D008862:Microsomes, Liver; D051381:Rats; D013255:Steroid 21-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D003580:Cytochromes; D019392:Cytochrome P-450 CYP2E1; C017170:Cyp1a2 protein, rat; C089877:Cyp2c6v1 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D013255:Steroid 21-Hydroxylase