Pharmacometrics of pterostilbene:: Preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity
Pharmacometrics of pterostilbene:: Preclinical pharmacokinetics and metabolism, anticancer, antiinflammatory, antioxidant and analgesic activity
复制标题
DOI：
10.1002/ptr.2277
复制
发表时间：
2008-02-01
影响因子：
7.2
通讯作者：
Davies, Neal M.
中科院分区：
文献类型：
--
作者：
Remsberg, Connie M.;Yanez, Jaime A.;Davies, Neal M.
本研究评价了反式紫檀芪，一些植物的成分的临床前药代动力学和药效学。对右颈静脉插管的雄性Sprague-Dawley大鼠静脉内给予20 mg/kg紫檀芪，并通过反相HPLC方法分析样品。血清AUC、血清t（1/2）、尿液t（1/2）、CI总和Vd（β）分别为17.5 ± 6.6 μ g/h/mL、1.73 ± 0.78 h、17.3 ± 5.6 h、0.960 ± 0.025 L/h/kg和2.41 ± 1.13 L/kg（平均值± SEM）。在血清和尿液中均检测到紫檀芪葡萄糖醛酸化代谢物。大鼠肝微粒体中的体外代谢进一步表明紫檀芪的II相代谢。紫檀芪在5种癌细胞系中表现出浓度依赖性抗癌活性（1-100 μ g/mL）。体外结肠炎模型显示HT-29细胞培养基中PGE（2）产生的浓度依赖性抑制。通过在犬软骨细胞中诱导炎症，然后用紫檀芪（1-100 μ g/mL）处理来检查抗炎活性。结果显示，与对照水平相比，MMP-3、sGAG和TNF-α的水平降低。紫檀芪表现出浓度依赖性的抗氧化能力的ABTS方法测量。紫檀芪增加反应的潜伏期在甩尾和热板镇痛试验。版权所有（C）2007约翰威利父子有限公司
The present study evaluated the preclinical pharmacokinetics and pharmacodynamics of trans-pterostilbene, a constituent of some plants. Right jugular vein cannulated male Sprague-Dawley rats were dosed i.v. with 20 mg/kg of pterostilbene and samples were analysed by the reverse phase HPLC method. Serum AUC, serum t(1/2), urine t(1/2), CItotal and Vd(beta) were 17.5 +/- 6.6 mu g/h/mL, 1.73 +/- 0.78 h, 17.3 +/- 5.6 h, 0.960 +/- 0.025 L/h/kg and 2.41 +/- 1.13 L/kg (mean +/- SEM), respectively. A pterostilbene glucuronidated metabolite was detected in both serum and urine. The in vitro metabolism in rat liver microsomes furthermore suggests phase II metabolism of pterostilbene. Pterostilbene demonstrated concentration-dependent anticancer activity in five cancer cell lines (1-100 mu g/mL). An in vitro colitis model showed concentration-dependent suppression of PGE(2) production in the media of HT-29 cells. Antiinflammatory activity was examined by inducing inflammation in canine chondrocytes followed by treatment with pterostilbene, (1-100 mu g/mL). The results showed decreased levels of MMP-3, sGAG and TNF-alpha compared with control levels. Pterostilbene exhibited concentration-dependent antioxidant capacity measured by the ABTS method. Pterostilbene increased the latency period to response in both tail-flick and hot-plate analgesic tests. Copyright (C) 2007 John Wiley & Sons, Ltd.