title: Investigating herb-herb interactions: the potential attenuated toxicity mechanism of the combined use of Glycyrrhizae radix et rhizoma (Gancao) and Sophorae flavescentis radix (Kushen).
abstract: BACKGROUND
  Glycyrrhizae radix et rhizoma (Gancao) is often prescribed together with Sophorae flavescentis radix (Kushen) in traditional Chinese medicinal practice to increase the efficacy on the treatment of hepatitis and hepatic fibrosis. Meanwhile, long-term single used Gancao can cause adverse reactions, lead to pseudohypercorticosteroidism especially. But the side effects of Gancao are significantly reduced when combined with Kushen; the reasons are still unknown. The aim of this study was to elucidate potential pharmacokinetic interaction between Kushen and Gancao, and to provide guidance for clinical medicine safety.
  
  
  METHODS
  A specific and rapid HPLC-MS method was established to quantify the four main activity ingredients matrine (MT), oxymatrine (OMT), glycyrrhizin (GL) and glycyrrhetinic acid (GA) in rat plasma. In this study, the pharmacokinetic parameters and the pharmacokinetic differences of the four main activity ingredients MT, OMT, GL and GA in single herb and Kushen-Gancao couple were obtained.
  
  
  RESULTS
  Compared with oral administration of Gancao extract, K10 and Tmax of GA significantly increased to 0.43 h(-1)and 30 h after giving Kushen-Gancao (p < 0.05), but T1/2 and Vd were reduced to 0.73 L kg(-1)and 4.98 h (p < 0.05). In addition, the AUC of GA was increased, and the other three activity ingredients all decreased.
  
  
  CONCLUSIONS
  GA as the main factor leading to the sodium-water retention side effects of Gancao. The result found that the absorption of GA was significantly slowed down and the metabolism rate was accelerated in Kushen-Gancao than single herb. So the attenuated toxicity mechanism may be because the accumulation of GA reduced in vivo. The conclusion has important meaning to the compatibility of Chinese med.
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Dang
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Qinhui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Renji Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai 200127, PR China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Renji Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai 200127, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Linna
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: XinYou
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of head!--td:Pharmacy,-->Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D006035:Glycyrrhiza / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D029909:Sophora / Q000737:chemistry
chemical_list: D004365:Drugs, Chinese Herbal; C494416:kushen
keywords: Attenuated toxicity; Glycyrrhetinic acid (Pubchem CID:10114); Glycyrrhizae radix et rhizome; Glycyrrhizin (Pubchem CID:14982); Herb–herb interactions; Matrine (Pubchem CID:91466); Oxymatrine (Pubchem CID:114850); Sophorae flavescentis radix