title: Potentiation of the anticoagulation effect of warfarin by the herbal remedy Shu-Jing-Hwo-Shiee-Tang in rats: The dosing regimen and pharmacokinetic interaction.
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 (WS22-h post), but not co-treatment (WS2co), decreased warfarin clearance and increased the maximal plasma concentration and the area under the curve (AUC0-t, AUC0-∞) of plasma concentration versus time of warfarin administration. S2 and S3 did not change the coagulation parameters. At 24 h after warfarin administration, the WS22-h postand WS32-h postgroups 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.
authors.affiliation: 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. Electronic address: ueng@nricm.edu.tw.
authors.forename: Yune-Fang
authors.initials: YF
authors.lastname: Ueng
authors.affiliation: 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.
authors.forename: Chung-Kuang
authors.initials: CK
authors.lastname: Lu
authors.affiliation: School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan, ROC; Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Sien-Hung
authors.initials: SH
authors.lastname: Yang
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hong-Jaan
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Divisions of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, ROC.
authors.forename: Chiung-Chiao
authors.initials: CC
authors.lastname: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D004365:Drugs, Chinese Herbal; C587906:shu-jing-hwo-shiee-tang; D014859:Warfarin
keywords: Coagulation time; Pharmacokinetics; Rat; Shu-Jing-Hwo-Shiee-Tang; Warfarin hydroxylation