Lab Anim Res.  2017 Sep;33(3):223-230. 10.5625/lar.2017.33.3.223.

Preclinical safety assessment of Angelica acutiloba using a 13-week repeated dose oral toxicity study in rats

  • 1Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, Korea.
  • 2Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
  • 3Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
  • 5Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Korea.
  • 6Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 7Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Korea.


Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide as a traditional herbal medicine with several bioactivities including anti-diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity. However, there is lack of toxicological data available to evaluate potential long-term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in accordance with the test guidelines published by the Organization for Economic Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse effects on mortality, body weight change, clinical signs, and organ weights was found following repeat oral administration to rats for 14 days (125, 250, 500, 1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest recommended dose of AA extract for the 13-week repeat-dose oral toxicity study. In the 13-week repeat-dose oral toxicity study, the AA extract was orally administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg body weight) to compare between control and AA extract groups. The administration of AA extract did not produce mortality or remarkable clinical signs during this 13-week study. And, the data revealed that there were no significant differences in food/water consumption, body weight, hematological parameters, clinical chemistry parameters, gross macroscopic findings, organ weight and histopathology in comparison to the control group. On the basis of these results, the subchronic NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And, the AA extract is considered safe to use orally as a traditional herbal medicine.


Angelica acutiloba; traditional medicine; toxicity; subchronic

MeSH Terms

Administration, Oral
Asian Continental Ancestry Group
Body Weight
Body Weight Changes
Chemistry, Clinical
Herbal Medicine
Medicine, Traditional
No-Observed-Adverse-Effect Level
Organ Size
Organisation for Economic Co-Operation and Development


  • Figure 1 Effects of Angelica acutiloba extract on the body weight changes after oral administration in male and female rats for 14 days. Data expressed as means±SD.

  • Figure 2 Effects of Angelica acutiloba extract on the body weight changes after oral administration in male and female rats for 13 weeks. Data expressed as means±SD.

  • Figure 3 Effects of Angelica acutiloba extract on the daily food intake and water consumption after oral administration in male and female rats for 13 weeks. (A) Daily food intake. (B) Daily water consumption. Data expressed as means±SD. (*) indicates a significant difference relative to the control group (0 mg/kg) (P<0.05).


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