title: Effects of aescin on cytochrome P450 enzymes in rats.
abstract: BACKGROUND
  Aescin, the main active component found in extracts of horse chestnut (Aesculus hippocastanum) seed a traditional medicinal herb, is a mixture of triterpene saponins. It has been shown to be effective in inflammatory, chronic venous and edematous treatment conditions in vitro and in vivo, and is broadly used to treat chronic venous insufficiency. The purpose of this study was to find out whether aescin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied.
  
  
  METHODS
  A cocktail solution at a dose of 5mL/kg, which contained phenacetin (20mg/kg), tolbutamide (5mg/kg), chlorzoxazone (20mg/kg) and midazolam (10mg/kg), was given as oral administration to rats treated with a single dose or multiple doses of intravenous aescin via the caudal vein. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time RT-PCR was performed to determine the effects of aescin on the mRNA expression of CYP1A2, CYP2C9, CYP2E1 and CYP3A4 in rat liver.
  
  
  RESULTS
  Treatment with a single dose or multiple doses of aescin had inductive effects on rat CYP1A2, while CYP2C9 and CYP3A4 enzyme activities were inhibited. Moreover, aescin has no inductive or inhibitory effect on the activity of CYP2E1. The mRNA expression results were in accordance with the pharmacokinetic results.
  
  
  CONCLUSIONS
  Aescin can either inhibit or induce activities of CYP1A2, CYP2C9 and CYP3A4. Therefore, caution is needed when aescin is co-administration with some CYP1A2, CYP2C9 or CYP3A4 substrates in clinic, which may result in treatment failure and herb-drug interactions.
authors.affiliation: Wenzhou People's Hospital, Wenzhou 325000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shuang-li
authors.initials: SL
authors.lastname: Zheng
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: xuzhisheng1111@163.com.
authors.forename: Zhi-sheng
authors.initials: ZS
authors.lastname: Xu
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: xurenai1986@163.com.
authors.forename: Ren-ai
authors.initials: RA
authors.lastname: Xu
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002753:Chlorzoxazone / Q000493:pharmacokinetics / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004928:Escin / Q000493:pharmacokinetics / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006207:Half-Life; D041743:Herb-Drug Interactions; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D006993:Hypnotics and Sedatives; D007004:Hypoglycemic Agents; D009125:Muscle Relaxants, Central; D012333:RNA, Messenger; D004928:Escin; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D002753:Chlorzoxazone; D008874:Midazolam
keywords: Aescin; CYP; Cocktail; Herb-drug interaction; mRNA