title: Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products.
abstract: BACKGROUND
  Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF.
  
  
  METHODS
  For pharmacokinetic study, Sprague-Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75g/kg), FRA-, SFF-, and VPF-treated (2.7g/kg) groups, respectively. The serum contents of thrombin-antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI2) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer.
  
  
  RESULTS
  Significantly increased levels of Cmax, AUC, T1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals.
  
  
  CONCLUSIONS
  The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Ying-Ni
authors.initials: YN
authors.lastname: Pan
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Liang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Niu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Yan-Nian
authors.initials: YN
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tong
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Hua
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China; Center for Developmental Therapeutics, Seattle Children's Research Institute, Division of Gastroenterology and Hepatology, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98102, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Clinical Laboratory, Shenyang Military Region General Hospital, No. 83, Wenhua Road, Shenyang, China.
authors.forename: Dong-Ya
authors.initials: DY
authors.lastname: Meng
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China. Electronic address: liuxiaoqiu3388@126.com.
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000990:Antithrombin III; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D011464:Epoprostenol / Q000097:blood; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D065260:Frankincense / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood*; D011517:Prothrombin Time; D051381:Rats; D027561:Salvia miltiorrhiza; D013918:Thrombin Time; D014315:Triterpenes / Q000097:blood / Q000493:pharmacokinetics
chemical_list: C447943:11-keto-boswellic acid; D004365:Drugs, Chinese Herbal; D005338:Fibrin Fibrinogen Degradation Products; D014315:Triterpenes; C094432:acetyl-11-ketoboswellic acid; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C028972:dan-shen root extract; D000990:Antithrombin III; D005340:Fibrinogen; D011464:Epoprostenol; D010447:Peptide Hydrolases; D065260:Frankincense
keywords: 11-Keto-β-boswellic acid (KBA); 3-Acetyl-11-keto-β-boswellic acid (AKBA); Anticoagulatory effect; Frankincense; Pharmacokinetics; Processed Frankincense