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Effects of isorhamnetin on CYP3A4 and herb-drug interaction
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- Author:
- No author available
- Journal Title:
- Acta Pharmaceutica Sinica
- Issue:
- 8
- DOI:
- No doi available
- Key Word:
- 孕烷X受体;CYP3A4;药物相互作用;异鼠李素
Abstract： 观察异鼠李素对CYP3A4的转录激活、mRNA诱导及酶活性的影响,并对其在联合用药中的药物相互作用进行评价.在HepG2细胞中,采用瞬时共转染报告基因实验检测异鼠李素对PXR介导的CYP3A4的转录激活作用；荧光定量RT-PCR方法检测其对CYP3A4 mRNA的诱导作用；底物化学发光法检测其对细胞CYP3A4酶活性的影响；细胞增殖实验检测其对化疗药物伊立替康肝癌细胞毒性的影响.结果表明,异鼠李素(1、10及25 μmol·L 1)可以剂量依赖性通过激活PXR而诱导CYP3A4的转录,同时可剂量依赖性上调CYP3A4mRNA表达,但对CYP3A4酶活性无影响,对化疗药物伊立替康肝癌细胞毒作用也无影响.提示异鼠李素对CYP3A4 mRNA的诱导可能与PXR途径有关,并且可能不会干扰与其联用的其他药物的代谢.本研究可以为异鼠李素临床合理用药提供参考.
- [1]原海燕,李焕德.植物药-化疗药物相互作用的研究进展[J].2007,(18).
- [2]王宇光,王升启,高月.PXR受体调控的CYP3A诱导及其在药物代谢中的重要意义[J].2006,(1).
- [3]刘冬英,杨敏,祝慧娟,等.几种植物化学物对人孕烷X受体介导的细胞色素P450 3A4转录调节作用[J].2006,(1).
- [4]刘彦锋,LI Hong-xing,颉欣妮,等.孕烷X受体的研究进展及其在药物代谢中的作用[J].2008,(14).
- [5]Yang J,Yan B.Photochemotherapeutic agent 8-methoxypsoralen induces cytochrome P450 3A4 and carboxylesterase HCE2: evidence on an involvement of the pregnane X receptor.[J].2007,95(1).
- [6]Edwige Van Der Heiden,Therese Sergent,Isabelle Dupont.CYP1 Al and CYP3A4 modulation by dietary flavonoids in human intestinal Caco-2 cells[J].2009,191(2).
- [7]Thomas K H, Chang.Activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) by herbal medicines.[J].2009,11(3).
- [8]Ding X,Staudinger JL,Lichti K.Pregnane X receptor and natural products: beyond drug-drug interactions.[J].2006,2(6).
- [9]Timsit YE,Negishi M.CAR and PXR: the xenobiotic-sensing receptors.[J].2007,72(3).
- [10]Stephen T, Smale.Luciferase assay.[J].2010,2010(5).
- [11]Matoney L,Zhu W,Zhang H,etc.Dexamethasone differentially regulates expression of carboxylesterase genes in humans and rats.[J].2000,28(2).
- [12]胡冰芳,毕惠嫦,黄民.孕烷X受体及组成性雄甾烷受体的研究新进展[J].2011,(10).
- [13]Cho YA,Burm JP,Choi JS.Effects of the antioxidant baicalein on the pharmacokinetics of nimodipine in rats: a possible role of P-glycoprotein and CYP3A4 inhibition by baicalein.[J].2011,63(4).
- [14]Yao X,Li Y,Wang Q.Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways.[J].2010,640(1).
- [15]Schellens JH,Harmsen S,Beijnen JH,etc.Nuclear receptor mediated induction of cytochrome P450 3A4 by anticancer drugs: a key role for the pregnane X receptor.[J].2009,64(1).