Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea; Practical Research Division, Honam National Institute of Biological Resources, Mokpo-si, 58762, Republic of Korea.
Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea; Safety Research Team, Crop Protection Research Institute, FarmHannong Co., Ltd, Nonsan-si, 33010, Republic of Korea.
J Ethnopharmacol. 2021 Jun 28;274:113944. doi: 10.1016/j.jep.2021.113944. Epub 2021 Mar 9.
The root of Achyranthes bidentata Blume, Achyranthis Radix (AR), is used as a traditional medicine ingredient in East Asia. It has anti-inflammatory, anti-oxidative, and anti-diabetic activities.
In the present study, we aimed to evaluate the oral toxicity and genotoxicity of single-dose and 4-week repeated-doses of AR hot water extract (ARE), under the good laboratory practice principles.
For oral toxicity studies, SD rats (n = 5 per sex and group) were administered ARE at concentrations of 500, 1000, and 2000 mg/kg/day once (single dose) or once per day for 4 weeks (repeated dose). The non-clinical genotoxicity study consisted of bacterial reverse mutation using Escherichia coli (WP2 uvrA) and Salmonella typhimurium (TA98, TA100, TA1535, and TA1537), in vitro chromosomal aberration test with Chinese hamster lung cells (CHL/IU), and in vivo mouse bone marrow micronucleus test using bone marrow cells collected from male ICR mice (n = 5) that were orally administered ARE.
In the single-dose oral toxicity study, mortality and treatment-related changes in body weight were not observed throughout the study, and the lethal dose was estimated to be > 2000 mg/kg in rats. In the 4-week repeated-dose oral toxicity study, ARE did not induce significant changes in body weight, organ weight, food intake, or hematological and serum biochemical parameters in any group. In the bacterial reverse mutation test, ARE did not induce gene mutations in any tested strain. In the chromosomal aberration test, ARE did not cause chromosomal aberrations. The micronucleus test showed no significant increase in the number of micronucleated polychromatic erythrocytes or the mean ratio of polychromatic to total erythrocytes.
These results showed that ARE does not induce oral toxicity and genotoxicity in the in vivo and in vitro test systems.
牛膝的根，牛膝（AR），被用作东亚传统医学的一种成分。它具有抗炎、抗氧化和抗糖尿病作用。
在本研究中，我们旨在根据良好实验室规范原则，评估单次和 4 周重复剂量 AR 热水提取物（ARE）的口服毒性和遗传毒性。
对于口服毒性研究，SD 大鼠（每组 5 只，雌雄各半）给予浓度为 500、1000 和 2000mg/kg/天的 ARE，单次（单次剂量）或每天一次，共 4 周（重复剂量）。非临床遗传毒性研究包括使用大肠杆菌（WP2 uvrA）和鼠伤寒沙门氏菌（TA98、TA100、TA1535 和 TA1537）进行细菌反向突变、中国仓鼠肺细胞（CHL/IU）体外染色体畸变试验以及使用雄性 ICR 小鼠（n=5）骨髓细胞进行体内小鼠骨髓微核试验口服给予 ARE。
在单次口服毒性研究中，整个研究过程中未观察到死亡率和与治疗相关的体重变化，估计大鼠的致死剂量>2000mg/kg。在 4 周重复口服毒性研究中，ARE 未引起任何组的体重、器官重量、食物摄入或血液学和血清生化参数的显著变化。在细菌反向突变试验中，ARE 未引起任何测试菌株的基因突变。在染色体畸变试验中，ARE 未引起染色体畸变。微核试验显示多染红细胞微核数或多染红细胞与总红细胞的平均比值无显著增加。
这些结果表明，ARE 在体内和体外试验系统中均不会引起口服毒性和遗传毒性。
