Evaluation of acute, 28-day, 13-week repeated dose oral toxicity and genotoxicity of a herbal extract (HemoHIM G) from Angelica sinensis, Ligusticum chuanxiong, and Peaonia lactiflora

Abstract

HemoHIM G is a functional food ingredient composed of a triple herbal combination of Angelica sinensis, Ligusticum chuanxiong, and Paeonia lactiflora, to improve impaired immune function. Considering the pharmacological benefits of its constituent herbal components, HemoHIM G is anticipated to have various health benefits; however, its toxicity has not been thoroughly evaluated. Here, we conducted a comprehensive study to assess the safety of HemoHIM G in terms of acute oral toxicity, 13-week repeat-dose toxicity, and genotoxicity. In the oral acute toxicity study, Sprague-Dawley rats were orally administered a single dose of HemoHIM G at 5000 mg/kg/day, the limit dose for the acute study. No abnormal findings or adverse effects were observed in this study, as confirmed by gross pathology. A 13-week repeated-dose toxicity study was conducted with HemoHIM G at doses of 1250, 2500, and 5000 mg/kg/day to examine the subchronic toxicity in both male and female rats after 28 days of dose-range finding study. No test substance-related clinical signs or mortality was observed at any of the tested doses. Gross pathology, hematology, blood chemistry, and histopathology were within normal ranges, further supporting the safety of HemoHIM G. Therefore, the NOAEL of HemoHIM G was considered to be at 5000 mg/kg/day for both sexes of rats. Bacterial reverse mutation tests, a chromosome aberration test in human peripheral blood lymphocytes, and a mouse micronuclei test were conducted to identify the potential genotoxicity of HemoHIM G. HemoHIM G is non-mutagenic and non-clastogenic. Collectively, these findings provide valuable evidence for the safe use of HemoHIM G as a functional food ingredient.

Keywords: Acute toxicity; Functional food; Genotoxicity; HemoHIM G; Repeat dose toxicity.

Fig. 1

A Mean body weights and B Mean feed consumption in 28-day repeated dose oral toxicity. HemoHIM G was administered to rats at graduated dose levels: 0 mg/kg/day (G1), 1250 mg/kg/day (G2), 2500 mg/kg/day (G3), and 5000 mg/kg/day (G4)

Fig. 2

Mean body weights in A male and B female SD rats, and C mean feed consumption in 13-week repeated dose oral toxicity. HemoHIM G was administered to rats at graduated dose levels, including a control group (G1) receiving 0 mg/kg/day, and treatment groups (G2-4) receiving doses of 1250, 2500, 5000 mg/kg/day, respectively