title: Pharmacokinetic profiles of the five isoflavonoids from Pueraria lobata roots in the CSF and plasma of rats.
abstract: BACKGROUND
  Traditional Chinese medicine Radix Puerariae, the roots of Pueraria lobata (Wild.) Ohwi., has been widely used for the treatment of cardiovascular and cerebrovascular diseases in China for centuries. Isoflavonoids are believed the active components of this herb.
  
  
  OBJECTIVE
  The present study aims to investigate the brain penetration and pharmacokinetics of five active isoflavonoids in the ventricular CSF and plasma of rats after intravenous administration of a Pueraria isoflavonoids (PIF) extract, to better understand the active components of this herb for neuro-activities.
  
  
  METHODS
  Under anesthesia condition, SD rats (n=6) were successively suffered two surgeries for implanting cannulas at lateral ventricle and right jugular vein for brain microdialysis and blood collection, respectively. After recovery, the rats received intravenous dose of PIF at 80mg/kg and the concentrations of puerarin (PU), 3'-methoxypuerarin (MPU), 3'-hydroxypuerarin (HPU), daidzein (DA) and daidzein-8-C-apiosyl-(1-6)-glycoside (DAC) in the ventricular dialysate and plasma samples were determined using a ultra-fast liquid chromatography tandem mass spectrometry method.
  
  
  RESULTS
  Complete concentration versus time profiles of the five components in plasma and four components except for HPU in ventricular CSF were obtained. After dosing, the average C0 values of PU, MPU, DA, DAC and HPU in plasma were estimated 6.53, 13.72, 1.54, 15.84 and 86.07µg/mL, and PU, MPU, DA and DAC were rapidly penetrated to the brain and reached to their Cmax of 521.52, 415.00, 74.34 and 380.03ng/mL in CSF at about 0.5-0.8h, respectively. The elimination t1/2 of PU, DA and DAC in CSF and plasma were no significant difference, while the t1/2 of MPU in ventricular CSF was longer than that in plasma which may attributable to the different physiological environment of central and peripheral compartments. The brain penetration index (AUCCSF/AUCplasma) was found to be about 9.29, 7.25, 11.96, and 4.21% for PU, MPU, DA, and DAC respectively.
  
  
  CONCLUSIONS
  PU, MPU, DA, DAC can quickly penetrate to the brain through the blood brain barrier (BBB) and might be responsible for the neuro-pharmacological activities of P. lobata.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China; Department of Pharmacy, The First People's Hospital of Lianyungang, Lianyungang 222002, PR China.
authors.forename: Bing-Xin
authors.initials: BX
authors.lastname: Xiao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Fang-Rui
authors.initials: FR
authors.lastname: Cao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Rui-Le
authors.initials: RL
authors.lastname: Pan
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, PR China. Electronic address: qchang@implad.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007529:Isoflavones / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D018517:Plant Roots; D029908:Pueraria; D017207:Rats, Sprague-Dawley
chemical_list: D007529:Isoflavones
keywords: Brain microdialysis; Isoflavonoids; Pharmacokinetics; Plasma; Pueraria lobata; UFLC-MS/MS