Preclinical safety assessment ofAngelica acutilobausing a 13-week repeated dose oral toxicity study in rats

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.

Angelica acutiloba Exerts Antihypertensive Effect and Improves Insulin Resistance in Spontaneously Hypertensive Rats Fed with a High-Fat Diet

“…As a result, we showed that AAE at a dose of 800 mg/kg/day had some beneficial effects in HFD-fed SHRs. Yun et al [27] reported that no adverse effects were shown even at a dose of 2,000 mg/kg/day in the 13-week repeat-dose oral toxicity study in rat. Therefore, it is possible to use more amounts of AAE to obtain better results.…”

In vivo and in vitro safety evaluation of fermented Citrus sunki peel extract: acute and 90-day repeated oral toxicity studies with genotoxicity assessment

“…5-Week old animals were purchased from Orient Bio Inc. (Gyeonggi-do, Korea) and only healthy animals were used in the study after two-week acclimation. As previously described [ 20 ], animals were housed in polycarbonate cages containing aspen bedding materials in an environment-controlled animal room at the AAALAC International-accredited animal facility (#001160) of Seoul National University Hospital. Animals were provided with sterilized laboratory rodent diet (LabDiet 5002, PMI Nutrition International) and autoclaved water at libitum .…”

“…5-Week old animals were purchased from Orient Bio Inc. (Gyeonggi-do, Korea) and only healthy animals were used in the study after two-week acclimation. As previously described [20], animals were housed in polycarbonate cages containing aspen bedding materials in an environment-controlled animal room at the AAAL AC International-accredited animal facility (#001160) [21]. Our toxicity studies were performed in compliance with the relevant OECD test guidelines [22][23][24][25][26] and Good Laboratory Practice regulations published by Korea Food Drug Administration [27].…”