title: Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.
abstract: Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY.
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, The Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Tao
authors.affiliation: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China. Electronic address: zhouhuam@hotmail.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai 201203, China; Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, 528 Zhangheng Road, Shanghai 201203, China. Electronic address: chenghailiu@hotmail.com.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000678:Amygdalin / Q000032:analysis / Q000097:blood*; D000818:Animals; D019540:Area Under Curve; D001572:Benzofurans / Q000032:analysis / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002934:Cinnamates / Q000032:analysis / Q000493:pharmacokinetics; D053630:Depsides / Q000032:analysis / Q000493:pharmacokinetics; D004365:Drugs, Chinese Herbal / Q000032:analysis* / Q000493:pharmacokinetics*; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism; D007773:Lactates / Q000032:analysis / Q000493:pharmacokinetics; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution; D000097123:Rosmarinic Acid
chemical_list: D000678:Amygdalin; D001572:Benzofurans; D002934:Cinnamates; D053630:Depsides; D004365:Drugs, Chinese Herbal; D007773:Lactates; D000097123:Rosmarinic Acid; C532829:fuzheng huayu; C035055:3,4-dihydroxyphenyllactic acid; C076944:salvianolic acid B
keywords: Fuzheng Huayu recipe; Hepatic fibrosis; Pharmacokinetics; Tissue distribution; UHPLC–MS/MS