中药舒筋活血汤增强大鼠华法林抗凝作用：给药方案及药代动力学相互作用

Potentiation of the anticoagulation effect of warfarin by the herbal remedy Shu-Jing-Hwo-Shiee-Tang in rats: The dosing regimen and pharmacokinetic interaction.

作者信息

Ueng Yune-Fang, Lu Chung-Kuang, Yang Sien-Hung, Wang Hong-Jaan, Huang Chiung-Chiao

机构信息

Divisions of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC; Department of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Institute of Biopharmaceutical Sciences, School of Pharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, ROC; Institute of Medical Sciences, School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.

Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC; Department of Life Sciences and Institute of Genome Sciences, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.

出版信息

Drug Metab Pharmacokinet. 2017 Feb;32(1):85-91. doi: 10.1016/j.dmpk.2016.11.010. Epub 2016 Dec 8.

DOI:10.1016/j.dmpk.2016.11.010

PMID:28111103

Abstract

The herbal remedy Shu-Jing-Hwo-Shiee-Tang (SJHST) has been used in traditional Chinese medical care for the treatment of osteoarthritis. This study aims to examine the influence of SJHST on the oxidation and anticoagulation effect of warfarin in male rats. In three SJHST preparations (S1-S3), hesperidin, gentiopicrin, and paeoniflorin were identified as chemical marker ingredients. The inhibition of liver microsomal warfarin 7-hydroxylation (WOH) activity by 50% methanolic extracts of SJHST was potentiated by β-glucosidase pretreatment, but not by NADPH-fortified microsomal preincubation. Among various ingredients and their β-glucosidase-hydrolyzed products, hesperetin caused the most potent inhibition of WOH. Oral administration of S2 to rats at 2 h after warfarin treatment (WS2), but not co-treatment (WS2), decreased warfarin clearance and increased the maximal plasma concentration and the area under the curve (AUC, AUC) of plasma concentration versus time of warfarin administration. S2 and S3 did not change the coagulation parameters. At 24 h after warfarin administration, the WS2 and WS3 groups had a prothrombin time longer than that of the warfarin group. These results demonstrate that a 2-h post-treatment of rats with SJHST caused pharmacokinetic interaction with warfarin, resulting in prothrombin time prolongation.

摘要

中药方剂舒筋活络汤（SJHST）已被用于中医治疗骨关节炎。本研究旨在探讨SJHST对雄性大鼠华法林氧化和抗凝作用的影响。在三种SJHST制剂（S1 - S3）中，橙皮苷、龙胆苦苷和芍药苷被鉴定为化学标记成分。SJHST的50%甲醇提取物对肝微粒体华法林7 - 羟化（WOH）活性的抑制作用在经β - 葡萄糖苷酶预处理后增强，但经NADPH强化的微粒体预孵育后未增强。在各种成分及其β - 葡萄糖苷酶水解产物中，橙皮素对WOH的抑制作用最强。在华法林治疗后2小时给大鼠口服S2（WS2），而非联合给药（WS2），降低了华法林清除率，增加了华法林给药后血浆浓度-时间曲线的最大血浆浓度和曲线下面积（AUC，AUC）。S2和S3未改变凝血参数。在华法林给药后24小时，WS2和WS3组的凝血酶原时间长于华法林组。这些结果表明，大鼠在华法林治疗后2小时给予SJHST会与华法林发生药代动力学相互作用，导致凝血酶原时间延长。