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学科主题: 物理化学
题名: Inhibitory Effects of Dibenzocyclooctadiene lignans from Fructus schisandrae on CYP2C8-mediated Paclitaxel Metabolism in Human Liver Microsomes
作者: Zhang YY(张延延) ;  Yang L(杨凌)
会议名称: 3rd Asian Pacific Regional Meeting of the International-Society-for-the-Study-of-Xenobiotics
会议日期: 2009-5-10
出版日期: 2009-05-10
会议地点: THAILAND
其他题名: 五味子木脂素成分对CYP2C8介导的紫杉醇代谢抑制作用
通讯作者: 杨凌
ISSN: 0360-2532
部门归属: 十八室
摘要: Inhibitory Effects of Dibenzocyclooctadiene Lingans from Fructus Schisandrae on CYP2C8-Mediated Paclitaxel Metabolism in Human Liver Microsomes Yan-Yan Zhang, Ling Yang Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, 116023 China Dibenzocyclooctadiene lingans are the principle active ingredients of Fructus Schisandrae, which is extensively used as an antitussive, sedative and tonic agent in China, Korea, Japan and Russia. According to Chinese Pharmacopoeia 2005 edition, these lingans are recognized as the major constituents in this Chinese herb medicine. Recently, schisandra extract and some purified lingans have been found to enhance the efficacy of paclitaxel against multidrug resistance tumor cell lines1. In the present study, an in vitro study was undertaken to evaluate the influence of 7 major Schisandra lingans on CYP2C8, which is the primary metabolic enzyme for paclitaxel. Among all these components, gomisin G (IC50=4.3±0.7 µM) exhibited the most potent inhibitory effect on CYP2C8-dependent paclitaxel 6α-hydroxylation in noncompetitive manner, with apparent Ki value of 4.1 µM. Gomisin A (IC50= 8.7±0.8 µM, Ki=8.6 µM) and pregomisin (IC50= 9.3±0.8 µM, Ki=8.0 µM) were also found to potently inhibit CYP2C8 in noncompetitive and competitive manner, respectively. However, schizandrol A (IC50>100 µM), schizandrin A (IC50= 31.8±1.7 µM), B (IC50= 12.6±1.9 µM) and C (IC50>100 µM) were considered less likely to cause drug-drug interactions via inhibition of CYP2C8 activity. Since paclitaxel holds a complex pharmacological and toxicological profile with a narrow therapeutic window2, special attention should be taken on the alteration of paclitaxel pharmacokinetic behavior, when coadministered with the corresponding dibenzocyclooctadiene lingans or the crude extract of Fructus Schisandrae. Reference 1. Huang M, Jin J, Sun H, Liu GT. Reversal of P-glycoprotein-mediated multidrug resistance of cancer cells by five schizandrins isolated from the Chinese herb Fructus Schizandrae. Cancer Chemother Pharmacol 2008 62(6):1015-1026. 2. Mielke S, Sparreboom A, Steinberg SM, Gelderblom H, Unger C, Behringer D, Mross K. Association of Paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer. Clin Cancer Res 2005 11(13): 4843-4850.
语种: 中文
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内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/113562
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Zhang YY,Yang L. Inhibitory Effects of Dibenzocyclooctadiene lignans from Fructus schisandrae on CYP2C8-mediated Paclitaxel Metabolism in Human Liver Microsomes[C]. 见:3rd Asian Pacific Regional Meeting of the International-Society-for-the-Study-of-Xenobiotics. THAILAND. 2009-5-10.
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