title: Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis.
abstract: OBJECTIVE
  To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.
  
  
  METHODS
  Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.
  
  
  RESULTS
  The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P< 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P< 0.05), while there was no statistical difference in the MG and HDG.
  
  
  CONCLUSIONS
  DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Ren
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Xian-Lin
authors.initials: XL
authors.lastname: Zhao
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Li
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wu
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Su
authors.affiliation: Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Wen-Fu
authors.initials: WF
authors.lastname: Tang
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000880:Anthraquinones / Q000493:pharmacokinetics; D001219:Aspartate Aminotransferases / Q000097:blood; D001713:Biphenyl Compounds / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004642:Emodin / Q000493:pharmacokinetics; D044950:Flavanones / Q000493:pharmacokinetics; D006569:Hesperidin / Q000493:pharmacokinetics; D007249:Inflammation; D017705:Lignans / Q000493:pharmacokinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D000880:Anthraquinones; D001713:Biphenyl Compounds; C551430:Da-Cheng-Qi; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D017705:Lignans; C005498:magnolol; C518327:aloe emodin; D006569:Hesperidin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C005273:naringenin; D004642:Emodin; C027113:chrysophanic acid; C005274:naringin; C020491:rhein
keywords: Acute liver injury; Acute pancreatitis; Da-Cheng-Qi decoction; Pharmacodynamics; Pharmacokinetics