title: Relationships between pharmacokinetics and efficacy of Xie-xin decoction in rats with experimental ulcerative colitis.
abstract: BACKGROUND
  Xie-xin decoction (XXD) has been used as a classic formula in China for the treatment of gastrointestinal dysfunction such as ulcerative colitis (UC). However, no potential action mechanisms and active compounds had been systematically investigated.
  
  
  OBJECTIVE
  To explore the effectiveness and the material basis of XXD in trinitrobenzene sulfonic acid (TNBS)-induced UC rats.
  
  
  METHODS
  XXD was administered orally for 8 days at a dosage of 2 or 4g/kg/day. Plasma pharmacokinetic properties and colon tissue concentrations of multiple compounds from XXD were detected. Tissue damage scores, production of interleukin (IL)-10 and myeloperoxidase (MPO), expression of tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa Bp65 (NF-κBp65) in colon tissues were examined. Canonical correlation analysis was performed to evaluate the relationships between pharmacokinetics and efficacy to elucidate significantly active compounds of XXD.
  
  
  RESULTS
  XXD promoted the recovery of colitis and inhibited the colonic inflammation damage in UC rats by reducing the level of MPO and the expression of TNF-α and NF-κBp65, and increasing the production of IL-10 in colon tissues. Efficacy of XXD was positively related with AUC of five plasma compounds (baicalin, berberine, wogonoside, wogonin, and rhein) and concentrations of six colon tissue compounds (coptisine, jatrorrhizine, palmatine, berberine, baicalein and emodin), respectively.
  
  
  CONCLUSIONS
  The multiple compounds in plasma and colon tissues from XXD might be the main material basis for therapeutic potentials in UC rats.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Han
authors.forename: Jie
authors.initials: J
authors.lastname: Zhong
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Du
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Shen
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Ma
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C518364:Xiexin decoction; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase