title: Synergistic effects of rhubarb-gardenia herb pair in cholestatic rats at pharmacodynamic and pharmacokinetic levels.
abstract: BACKGROUND
  Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb-gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels.
  
  
  METHODS
  Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α-naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC-MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma.
  
  
  RESULTS
  The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone.
  
  
  CONCLUSIONS
  The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP.
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Lei-Chi
authors.initials: LC
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Ya-Xi
authors.initials: YX
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), No. 24 Tongjia Lane, Nanjing 210009, China. Electronic address: cpuli@163.com.
authors.forename: Hui-Jun
authors.initials: HJ
authors.lastname: Li
mesh_terms: D015058:1-Naphthylisothiocyanate; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000880:Anthraquinones / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D004642:Emodin / Q000097:blood; D005638:Fruit; D032062:Gardenia; D039823:Iridoids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D020011:Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012250:Rheum; D027343:Rhizome
chemical_list: D000880:Anthraquinones; D039823:Iridoids; D010936:Plant Extracts; D020011:Protective Agents; D015058:1-Naphthylisothiocyanate; C007834:genipin; C518327:aloe emodin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D004642:Emodin; C027113:chrysophanic acid; D001663:Bilirubin; C020491:rhein
keywords: 1,8-dihydroxyanthraquinone (PubChem CID: 2950); Aloe emodin (PubChem CID: 10207); Chrysophanol (PubChem CID: 10208); Emodin (PubChem CID: 3220); Genipin (PubChem CID: 442424); Geniposide (PubChem CID: 107848); Hepatoprotectivity; Pharmacodynamics; Pharmacokinetics; Rhein (PubChem CID: 10168); Rhubarb-gardenia herb pair; Synergistic effects