title: Astragaloside IV inhibited the activity of CYP1A2 in liver microsomes and influenced theophylline pharmacokinetics in rats.
abstract: OBJECTIVE
  With the growing popularity of herbal and natural medicinal products, attention has turned to possible interactions between these products and pharmaceutical drugs. In this study, we examined whether astragaloside IV (AGS-IV) could inhibit the activity of CYP1A2 in rat liver microsomes in vitro and in vivo.
  
  
  METHODS
  The effect of AGS-IV on CYP1A2 activity was investigated using probe substrates: phenacetin in vitro and theophylline in vivo. Phenacetin was incubated in rat liver microsomes with or without AGS-IV, and the mechanism, kinetics and type of inhibition were determined. The inhibitory effect of AGS-IV on CYP1A2 activity in rats was also determined using theophylline in vivo. The pharmacokinetics of theophylline were observed after a single or week-long treatment with AGS-IV.
  
  
  RESULTS
  AGS-IV was found to be a competitive inhibitor with a K(i) value of 6.29 μM in vitro. In the multiple-pretreatment rat group, it was found to have a significantly higher area under the concentration-time curve (AUC) for theophylline, as well as a lower apparent oral total body clearance value (CL/F). In contrast, no significant difference in metabolism of theophylline was found for the single pretreatment group.
  
  
  CONCLUSIONS
  These findings suggest that AGS-IV is a potent inhibitor of CYP1A2. This work offers a useful reference for the reasonable and safe use of clinically prescribed herbal or natural products to avoid unnecessary herb-drug interactions.
authors.affiliation: Institute of Life Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Zhang
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Yan-Lei
authors.initials: YL
authors.lastname: Guo
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
mesh_terms: D000818:Animals; D027883:Astragalus Plant / Q000009:adverse effects / Q000737:chemistry; D027885:Astragalus propinquus; D001711:Biotransformation / Q000187:drug effects; D002681:China; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D020834:Ethnopharmacology; D006207:Half-Life; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010615:Phenacetin / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000009:adverse effects / Q000494:pharmacology*; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014315:Triterpenes / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D003580:Cytochromes; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; C027492:Huang Qi; D013806:Theophylline; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin