title: Increased involvement of Panax notoginseng in the mechanism of decreased hepatotoxicity induced by Tripterygium wilfordii in rats.
abstract: BACKGROUND
  The key problem with toxic Chinese herbs in clinical applications is how to find the most effective method to reduce toxicity. This study focuses on discussing the mechanism of decreased hepatotoxicity by the usage compatibility of two commonly used traditional Chinese drugs that are used clinically: Tripterygium wilfordii Hook. f. (TW) and Panax notoginseng (Burkill) F.H. Chen (PN). Additionally, based on the results from using metabonomics technology, the usage compatibility with these two herbs that was originated from clinical experience is the first to clarify the rationality of the drug combination.
  
  
  METHODS
  Through a fast and effective HPLC method, plasma concentration-time profiles and triptolide distribution characteristics in liver, heart, spleen, lung and kidney tissues were simultaneously determined in rats after oral administration of the aqueous extract of TW and TW-PN. The reduced hepatotoxicity data of the usage compatibility with TW and PN were also investigated, and then a UHPLC-QTOF/MS method was developed and validated for the explanation of the reduced hepatotoxicity mechanism.
  
  
  RESULTS
  It was indicated that nine endogenous metabolites might be potential biomarkers for hepatotoxicity induced by TW. In addition, the plasma concentration-time profiles and the distribution characteristics of TP in rats were changed after oral administration of the aqueous extract of TW-PN, and simultaneously, the hepatotoxicity was obviously decreased.
  
  
  CONCLUSIONS
  The results indicated that usage compatibility with TW and PN was reasonable in clinical use. To the best of our knowledge, this is the first report to describe the mechanism of reducing hepatotoxicity with the combined use of TW and PN from clinical experience.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Benyong
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qichun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Mengzhu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xinlong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Donglei
authors.initials: D
authors.lastname: Shi
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jinao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: Huaxu72@126.com.
authors.forename: Huaxu
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China. Electronic address: Zhouxp1960@163.com.
authors.forename: Xueping
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D008297:Male; D053723:Panax notoginseng / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010947:Plants, Toxic; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D029757:Tripterygium / Q000737:chemistry*
chemical_list: D010936:Plant Extracts
keywords: Mechanism of reducing hepatotoxicity; Metabonomics technology; Panax notoginseng; Pharmacokinetics characteristics; Tripterygium wilfordii; Usage compatibility