重齿毛当归(独活)中异当归醇、毛当归醇及其它香豆素的分离与鉴定

Nine coumarins were isolated from dichloromethane extract of the roots of Angelica pubescens Maxim. Seven of them were identified as osthol (Ⅰ), columbianetin acetate (Ⅱ), columbianetin (Ⅲ), bergapten (Ⅳ), angelol (Ⅴ),xanthotoxin (Ⅵ) and isoimperatorin (Ⅶ). (Ⅵ) and (Ⅶ) were isolated for the first time from this plant. Two new coumarins were elucidated as isoangelol (Ⅷ), a geometric isomer of angelol C₂₀H₂₄O₇ [α]_D²⁰-133.5 and anpubesol C₂₀H₂₆O₇ [α]_D²⁰ -72.5 on the basis of spectral evidences.     

重齿毛当归(独活)中异当归醇、毛当归醇及其它香豆素的分离与鉴定

独活为繖形科植物重齿毛当归Angelica pubescens MaXim.f.biserrata Shan et Yuan的根,为常用祛风湿药,具有祛风、除湿、止痛之功能,有关其化学成分研究较多,主要含欧芹酚甲醚等香豆素化合物,以酶、受体等指标进行筛选表明其二氯甲烷部分具有拮抗钙通道阻滞剂受体(nitrendipine rcceptor)活性,此活性与血压、心律有关,为研究其活性成分,     

Identification of cytochrome P4503A4 as the major enzyme responsible for the metabolism of ivermectin by human liver microsomes

1. Ivermectin was extensively metabolized by human liver microsomes to at least 10 metabolites. The structure of many of them (mostly hydroxylated and demethylated) was determined by ¹H-NMR and LC MS. 2. To determine which human cytochrome P450 isoform(s) is responsible for the metabolism of ivermectin, chemical inhibitors including sulphaphenazole, quinidine, furafylline, troleandomycin (TAO) and diethyldithiocarbamate (DDC) were used to evaluate their effect on ivermectin metabolism. TAO, a specific inhibitor of cytochrome P4503A4, was the most potent inhibitor, inhibiting the total metabolism as well as formation of each metabolite. Metabolismwas also inhibited byananti-humancytochrome 3A4 antibody by 90%. 3. When ivermectin was incubated with microsomes from cells expressing CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at 4?mg/ml protein concentrations, metabolic activity was only detected with the microsomes containing CYP3A4. The metabolic profile from cDNA-expressed CYP3A4 microsomes was qualitatively similar to that from human liver microsomes. 4. Thus, cytochrome P4503A4 is the predominant isoform responsible for the metabolism of ivermectin by human liver microsomes.