title: Acute and sub-chronic oral toxicity profiles of the aqueous extract of Cortex Dictamni in mice and rats.
abstract: BACKGROUND
  Cortex Dictamni is used in Chinese folk medicine for the treatment of jaundice, cough, rheumatism and some skin diseases; however, its possible toxicity has not been rigorously studied. The present investigation was carried out to evaluate the safety of Cortex Dictamni aqueous extract (CDAE) by acute and sub-chronic toxicity studies.
  
  
  METHODS
  In acute toxicity tests, seven groups of mice (n=5/group/sex) were orally treated with doses of 0, 28.7, 33.6, 39.7, 46.7, 54.9 and 64.6g/kg of CDAE and general behavior, adverse effects and mortality were recorded for up to 14 days. In sub-chronic toxicity assays, animals received CDAE by gavage at the doses of 0, 3.0, 6.0 or 12.0g/kg/day (n=10/group/sex) for 4 weeks and then followed for a 2-week recovery period. The biochemical, hematological and morphological parameters were determined.
  
  
  RESULTS
  In adult mice, single oral administrations of CDAE (0-64.6g/kg body weight) induced an increase in the incidence of general behavioral adverse effects. The mortality rate also increased with increasing dosage (LD50=48.2g/kg). In rats, daily single oral doses of CDAE were well tolerated behaviorally after 4 weeks and induced no significant changes in body weights. However, the absolute and relative liver weight at the end of both administration and recovery periods were significantly elevated, although the histological examination of various organs revealed no differences between the control and the treated groups. The hematological and biochemical parameters were significantly changed; lymphocytes, alanine transaminase, alkaline phosphatase levels showed a significant decrease while neutrophilic granulocyte, albumin, total cholesterol, glucose and blood urea nitrogen levels showed a significant increase, suggesting disturbances of hematopoiesis and liver and kidney functions.
  
  
  CONCLUSIONS
  Overall, the acute toxicity of CDAE was not clearly observed. However, it is possible that CDAE has a selective toxicity considering the changes in some hematological and liver function parameters and the liver-body weight ratios in the sub-chronic oral toxicity study.
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Kanion Pharmaceutical Co., Ltd., Lianyungang 222002, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; Pharmaceutical College of Henan University, Kaifeng 475001, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Kanion Pharmaceutical Co., Ltd., Lianyungang 222002, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Hiderori
authors.initials: H
authors.lastname: Arai
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China. Electronic address: vascular888@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027821:Rutaceae / Q000737:chemistry*; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D010936:Plant Extracts
keywords: Acute toxicity; Cortex Dictamni; Mice; Rats; Sub-chronic toxicity