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

Jun-Won Yun,Euna Kwon,Yun-Soon Kim,Jeong-Hwan Che,Seung-Hyun Kim,Byeong-Cheol Kang,In Ae Park,Ji-Ran You,Hyeon Hoe Kim

doi:10.5625/lar.2017.33.3.223

Abstract

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.

Highlights

Danggui, the root of the species Angelica belonging to the family Umbelliferae, has been named ‘female ginseng’ and has been most commonly used traditional herbal medicine for the treatment of gynecological disorders, such as menoxenia and anemia, due to its hemogenic, analgesic, and sedative activities [1,2,3]
All of the animal experiments were approved by the Institutional Animal Care and Use Committee of the Biomedical Research Institute at the Seoul National University Hospital, and this study was performed in compliance with the guidelines published by the Organization for Economic Cooperation and Development (OECD) as well as the guidance for Good Laboratory Practices for toxicity tests issued by the Ministry of Food and Drug Safety [25]
For the 13-week repeat-dose toxicity study, the hot water AA extract was administered to F344 rats (10/sex/group) by oral gavage at doses of 125, 250, 500, 1000, and 2000 mg/kg of body weight/10 mL distilled water (DW) once daily for 13 weeks in accordance with OECD guideline 408 [26] and the US National Toxicology Program (NTP) protocol

Summary

Introduction

The root of the species Angelica belonging to the family Umbelliferae, has been named ‘female ginseng’ and has been most commonly used traditional herbal medicine for the treatment of gynecological disorders, such as menoxenia and anemia, due to its hemogenic, analgesic, and sedative activities [1,2,3]. We investigated the subchronic repeated dose oral toxic effects of the AA extract in rats in the present study.

Results

Conclusion