Interaction of silymarin components and their sulfate metabolites with human serum albumin and cytochrome P450 (2C9, 2C19, 2D6, and 3A4) enzymes

Biomedicine & Pharmacotherapy

Kateřina Valentová¹  Beáta Lemli¹  Violetta Mohos¹  Zelma Faisal²  Kristýna Káňová²  Eszter Fliszár-Nyúl²  Sándor Kunsági-Máté³  Miklós Poór³ 

[1] János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary;Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Szigeti út 12, Pécs H-7624, Hungary;Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic;

关键词: Silymarin;    Sulfate conjugates;    Human serum albumin;    Cytochrome P450;    Pharmacokinetic interaction;    Herb-drug interaction;   

DOI  :  

来源: DOAJ

【 摘 要 】

Silymarin is a mixture of flavonolignans isolated from the fruit of milk thistle (Silybum marianum (L.) Gaertner). Milk thistle extract is the active ingredient of several medications and dietary supplements to treat liver injury/diseases. After the oral administration, flavonolignans are extensively biotransformed, resulting in the formation of sulfate and/or glucuronide metabolites. Previous studies demonstrated that silymarin components form stable complexes with serum albumin and can inhibit certain cytochrome P450 (CYP) enzymes. Nevertheless, in most of these investigations, silybin was tested; while no or only limited information is available regarding other silymarin components and metabolites. In this study, the interactions of five silymarin components (silybin A, silybin B, isosilybin A, silychristin, and 2,3-dehydrosilychristin) and their sulfate metabolites were examined with human serum albumin and CYP (2C9, 2C19, 2D6, and 3A4) enzymes. Our results demonstrate that each compound tested forms stable complexes with albumin, and certain silymarin components/metabolites can inhibit CYP enzymes. Most of the sulfate conjugates were less potent inhibitors of CYP enzymes, but 2,3-dehydrosilychristin-19-O-sulfate showed the strongest inhibitory effect on CYP3A4. Based on these observations, the simultaneous administration of high dose silymarin with medications should be carefully considered, because milk thistle flavonolignans and/or their sulfate metabolites may interfere with drug therapy.

【 授权许可】

Unknown