title: The dosage-toxicity-efficacy relationship of kansui and licorice in malignant pleural effusion rats based on factor analysis.
abstract: BACKGROUND
  The root of Euphorbia kansui T.P. Wang (Euphorbiaceae), a well-known traditional Chinese medicine (TCM) with certain toxicity, is known as Gan sui (Chinese: ) or kansui. It has been used to treat edema, ascites, asthma, and etc. Licorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza inflate Bat. or Glycyrrhiza glabra L., Leguminosae. It is a widely used herbal medicine native to southern Europe and parts of Asia as an herbal medicine and natural sweetener. Kansui cannot be co-used with licorice, which is recorded in "eighteen incompatible" medicaments in many monographs of TCM.
  
  
  OBJECTIVE
  The present study was conducted to investigate the dosage-toxicity-efficacy relationship of the co-use of kansui and licorice and to explore its regularity of the toxicity and efficacy change.
  
  
  METHODS
  Malignant pleural effusion rats were used and randomly divided into the normal control group, model group, positive control group (furosemide), kansui group, licorice group, and kansui-licorice groups with different ratios (kansui: licorice: 4:1, 2:1, 1:1, 0.5:1, 0.25:1, 0.1:1). Each group was adopted simultaneously to investigate the characteristic of toxicity and effect by measuring the pleural fluid and urine volumes, serum biochemical indexes, and serum TNF-α, IL-2 and IFN-γ levels. The factor analytic approach was used to analyze the dosage-toxicity-efficacy relationship between kansui and licorice.
  
  
  RESULTS
  Two common factors were extracted from 8 indexes concerning toxicity and 5 indexes concerning efficacy. And the total factors related to toxicity (Ft) and efficacy (Fe) were calculated. The curved line of Ft indicated that the toxicity was increased along with the dose increase in licorice. The curved line of Fe indicated that the efficacy was decreased along with the dose increase in licorice. The intersection of these two lines was between the ratios of 2:1 and 1:1, and was deemed the flex point of the dosage-toxicity-efficacy.
  
  
  CONCLUSIONS
  Kansui demonstrated a certain efficacy in treating malignant pleural effusion, and the efficacy could be weakened by the co-use of licorice, even causing serious toxicity at the given ratio. The ratio between 2:1 and 1:1 (kansui: licorice) was deemed the flex point of the dosage-toxicity-efficacy of kansui and licorice. The results will be helpful for their better utilization and development.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Shen
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Er-Xin
authors.initials: EX
authors.lastname: Shang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. Electronic address: yupingtang@njucm.edu.cn.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kai
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Cao
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Gui-Sheng
authors.initials: GS
authors.lastname: Zhou
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Tao
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: An
authors.initials: A
authors.lastname: Kang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Su
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Qian
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China. Electronic address: dja@njucm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D028481:Euphorbia; D005163:Factor Analysis, Statistical; D006035:Glycyrrhiza; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008517:Phytotherapy / Q000009:adverse effects; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity*; D018517:Plant Roots; D016066:Pleural Effusion, Malignant / Q000097:blood / Q000188:drug therapy*; D017208:Rats, Wistar; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D007376:Interleukin-2; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Dosage-toxicity-efficacy; Factor analysis; Kansui; Licorice; Malignant pleural effusion