title: Pharmacokinetic comparisons of two different combinations of Shaoyao-Gancao Decoction in rats: competing mechanisms between paeoniflorin and glycyrrhetinic acid.
abstract: BACKGROUND
  Shaoyao-Gancao Decoction (SGD), a well-known traditional Chinese medicine prescription, is a combination of Radix Paeoniae Alba (Paeonia lactiflora Pall, root) and Glycyrrhizae uralensis (Glycyrrhiza uralensis Fisch., root and rhizome, honeyed) for spasmolysis and emergency pain relief. Paeoniflorin (PF) and glycyrrhetinic acid (GA) are two typical active components of SGD for pain relief.
  
  
  OBJECTIVE
  To study comparative pharmacokinetics of ten bioactive compounds in SGDs with two different combinations of RP and GU, and therefore to investigate the herb-herb interaction mechanisms of Shaoyao-Gancao Decoction for better spasmolysis and emergency pain relief in rats.
  
  
  METHODS
  Herbal IR macro-fingerprinting was implemented to provide the full chemical fingerprints of RP, GU and SGD decoctions and to investigate the variation rule of the full chemical profile of SGDs with various combinations of RP and GU. A specifically developed HPLC-MS/MS assay coupled with protein precipitation method was employed to determine the plasma concentrations of the ten analytes. Male Wistar rats were orally administered with SGD1 (RP:GU, 1:1 (w/w)) and SGD2 ((RP:GU, 4:1 (w/w)) equivalent to 9.5 g/kg body weight of GU.
  
  
  RESULTS
  Full chemical fingerprints of RP, GU and SGDs with various combinations of RP and GU were provided in the form of IR macro-fingerprints. Except for liquiritin, there were statistically significant differences (p<0.05 or p<0.01) of these analytes between SGD1 and SGD2 in in vivo pharmacokinetic study. Compared with the results when oral administrated with SGD1, six glycosides (PF, albiflorin, oxypaeoniflorin, isoliquiritin, ononin, and glycyrrhizin) exhibited higher systematic exposure levels (AUC0-t) and slower elimination rates (CL) whereas two glycones (GA and isoliquiritigenin) were the reverse when administrated with SGD2.
  
  
  CONCLUSIONS
  Increasing the amount of RP attenuated the inhibitory effect of GA via competing being consumed by intestinal bacteria (or β-glucosidase) to reduce the conversion amount of glycyrrhizin to GA and subsequently to afford significantly higher bioavailability and longer efficacy of PF, glycyrrhizin, albiflorin, oxypaeoniflorin, isoliquiritin, and ononin, leading to better spasmolysis and emergency pain relief.
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing 100084, PR China. xuchanghua@gmail.com
authors.forename: Chang-Hua
authors.initials: CH
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Dong-Hua
authors.initials: DH
authors.lastname: Li
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Li
authors.forename: Su-Qin
authors.initials: SQ
authors.lastname: Sun
authors.forename: Xian-Zhong
authors.initials: XZ
authors.lastname: Wu
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics*; D044950:Flavanones / Q000032:analysis / Q000493:pharmacokinetics*; D005960:Glucosides / Q000032:analysis / Q000493:pharmacokinetics*; D041743:Herb-Drug Interactions; D008297:Male; D010276:Parasympatholytics / Q000737:chemistry / Q000493:pharmacokinetics; D053978:Pentacyclic Triterpenes / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005960:Glucosides; D010276:Parasympatholytics; D053978:Pentacyclic Triterpenes; C499903:jackyakamcho-tang
keywords: GA; GU; GZ; Glycyrrhetinic acid; Glycyrrhizae uralensis; HM; HPLC-MS/MS; PF; Paeoniflorin; RP; Radix Paeoniae Alba; SGD; Shaoyao-Gancao Decoction; glycyrrhenitic acid; glycyrrhizin; herbal medicine; paeoniflorin