Cui Yanyan, Ang Catharina Y W, Beger Richard D, Heinze Thomas M, Hu Lihong, Leakey Julian
National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Drug Metab Dispos. 2004 Jan;32(1):28-34. doi: 10.1124/dmd.32.1.28.
Hyperforin is an important active component of St. John's wort (Hypericum perforatum) that has been suggested to be responsible for the St. John's wort antidepressive effects and herbal-drug interactions. In this study, the in vitro metabolism profile of hyperforin was investigated using liver microsomes from male and female Sprague-Dawley rats, with or without induction by phenobarbital or dexamethasone. Four major Phase I metabolites, named 19-hydroxyhyperforin, 24-hydroxyhyperforin, 29-hydroxyhyperforin, and 34-hydroxyhyperforin, were isolated by high performance liquid chromatography and identified by mass spectrometry and NMR. Results suggest that hydroxylation is a major biotransformation of the hyperforin pathway in rat liver and that inducible cytochrome P450 3A (CYP450 3A) and/or CYP2B may be the major cytochrome P450 isoforms catalyzing these hydroxylation reactions.
金丝桃素是贯叶连翘（Hypericum perforatum）的一种重要活性成分，有人认为它是贯叶连翘产生抗抑郁作用以及发生草药-药物相互作用的原因。在本研究中，利用雄性和雌性斯普拉格-道利大鼠的肝微粒体，研究了金丝桃素在体外的代谢情况，肝微粒体分别经过或未经过苯巴比妥或地塞米松诱导。通过高效液相色谱法分离出四种主要的I相代谢产物，分别命名为19-羟基金丝桃素、24-羟基金丝桃素、29-羟基金丝桃素和34-羟基金丝桃素，并通过质谱和核磁共振进行鉴定。结果表明，羟基化是大鼠肝脏中金丝桃素代谢途径的主要生物转化方式，诱导型细胞色素P450 3A（CYP450 3A）和/或CYP2B可能是催化这些羟基化反应的主要细胞色素P450同工酶。
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