title: Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio-platycodin D in Jiegeng.
abstract: BACKGROUND
  Jiegeng (Radix Platycodi), the dried root of Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore throat, bronchitis, and bronchial asthma for thousands of years. It is commonly prescribed with Gancao (Radix et Rhizoma Glycyrrhizae) as a herbal combination in traditional Chinese medicine (TCM) to produce synergistic effects.
  
  
  OBJECTIVE
  To elucidate the herbaceous compatibility of Jiegeng and Gancao, we investigated the comparative pharmacokinetics, intestinal absorption, and microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the platycodins contained in Jiegeng.
  
  
  METHODS
  In the comparative pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE) and the Jiegeng-Gancao herb pair (JGHP) were determined in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, the main pharmacokinetic parameters were calculated using data analysis software (DAS). Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed to contradistinguish the intestinal absorption and microbial metabolism of PD and DPD in JE from those in JGHP.
  
  
  RESULTS
  The peak concentration (Cmax) and area under the plasma concentration curve (AUC) of PD in rats orally administrated JGHP significantly increased compared to that in rats treated with JE. In addition, the time to reach peak concentration (Tmax) and half-life (t1/2) of PD and DPD in combination with JGHP were all prolonged compared with those of JE. There was no significant difference in the absorption of PD between JE and JGHP in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker than that in JE after a 2-h incubation in fecal lysate which might be responsible for the different pharmacokinetic profiles of the platycodins in JE and JGHP.
  
  
  CONCLUSIONS
  In this study, we discovered that Gancao might influence the pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in profiles may be attributable to the inequable microbial metabolism rather than intestinal absorption of the platycodins in JE and JGHP. The results of this study elucidated the pharmacokinetic compatibility and rationale for the use of JGHP.
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, College of Pharmacy, Nanjing 210023, China. Electronic address: jshan@njucm.edu.cn.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Shan
authors.affiliation: Jiangsu Engineering Research Center for Efficient Delivery System of TCM, College of Pharmacy, Nanjing 210023, China; Changshu Hospital of Traditional Chinese Medicine, Changshu 215500, China.
authors.forename: Jia-Shuang
authors.initials: JS
authors.lastname: Zou
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xie
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, College of Pharmacy, Nanjing 210023, China.
authors.forename: An
authors.initials: A
authors.lastname: Kang
authors.affiliation: Jiangsu Engineering Research Center for Efficient Delivery System of TCM, College of Pharmacy, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jian-Ya
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Cun-Si
authors.initials: CS
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Shou-Chuan
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, College of Pharmacy, Nanjing 210023, China. Electronic address: diliuqing@hotmail.com.
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Di
mesh_terms: D000818:Animals; D019540:Area Under Curve; D018938:Caco-2 Cells; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018517:Plant Roots; D031238:Platycodon / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027343:Rhizome; D012503:Saponins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods; D014315:Triterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; C000593592:deapi-platycodin D; C108953:platycodin D
keywords: Absorption; Gancao; Liquid chromatography–tandem mass spectrometry; Metabolism; Pharmacokinetics; Platycodin