title: Metabolism of dl-praeruptorin A in rat liver microsomes using HPLC-electrospray ionization tandem mass spectrometry.
abstract: dl-Praeruptorin A (Pd-Ia) is the major active constituent of the traditional Chinese medicine Peucedanum praeruptorum Dunn. Recently it has been identified as a novel agent in the treatment and prevention of cardiovascular diseases. Accordingly, we investigated the metabolism of Pd-Ia in rat liver microsomes. The involvement of cytochrome P450 (CYP) and CYP isoforms were identified using a CYP-specific inhibitor (SKF-525A), CYP-selective inhibitors (α-naphthoflavone, metyrapone, fluvastatin, quinidine, disulfiram, ketoconazole and ticlopidine) and CYP-selective inducers (phenobarbital, dexamethasone and β-naphthoflavone). Residual concentrations of the substrate and metabolites were determined by HPLC, and further identified by their mass spectra and chromatographic behavior. These experiments showed that CYP450 is involved in Pd-Ia metabolism, and that the major CYP isoform responsible is CYP3A1/2, which acts in a concentration-dependent manner. Four Pd-Ia metabolites (M1, M2, M3, and M4) were detected after incubation with rat liver microsomes. Hydroxylation was the primary metabolic pathway of Pd-Ia, and possible chemical structures of the metabolites were identified. Further research is now needed to link the metabolism of Pd-Ia to its drug-drug interactions.
authors: College of Medical, Xiamen University, Xiamen 361005, China.
authors: Hang
authors: H
authors: Ruan
authors: Zhen
authors: Z
authors: Zhang
authors: Xin-fang
authors: XF
authors: Liang
authors: Yan
authors: Y
authors: Fu
authors: Mei-qin
authors: MQ
authors: Su
authors: Qi-lin
authors: QL
authors: Liu
authors: Xiu-min
authors: XM
authors: Wang
authors: Xuan
authors: X
authors: Zhu
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000378:metabolism* / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000032:analysis / Q000494:pharmacology; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D011335:Proadifen / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D002317:Cardiovascular Agents; D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C441070:praeruptorin A; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A