Acute toxicity and genotoxicity evaluation of hyperoside extracted from Abelmoschus manihot (L.) Medic  

黄蜀葵花提取物金丝桃苷的急性毒性和遗传毒性评价(英文)

作　　者：艾国[1,2] 黄正明[2] 王德文[1] 张海艇[3] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]解放军302医院药学部,北京100039 [3]山东大学新药评价中心,山东济南250100

出　　处：《Journal of Chinese Pharmaceutical Sciences》2012年第5期477-482,共6页中国药学（英文版）

基　　金：National Nature Science Foundation of China (Grant No.30572350);New Drug Foundation of State Administration of Traditional Chinese Medicine (Grant No.DIX005A)

摘　　要：To further assess hyperoside as a potential new anti-hepatitis B virus （HBV） drug, the safety of hyperoside extracted from Abelmoschus manihot （L.） Medic was evaluated by testing its acute toxicity and mutagenic risk. To test the acute toxicity of hyperoside, we determined the median lethal dose （LD 50 ） in mice. Forty healthy BALB/c mice （20 per sex） were administered a single oral dose of 5000 mg/kg hyperoside via the intragastrical route. The number of animals poisoned and died was noted daily for 14 consecutive days. All animals survived and appeared active and normal, indicating that the LD 50 of hyperoside was more than 5000 mg/kg. Potential genotoxicity of hyperoside was investigated using a bacterial reverse mutation assay （Ames test）, a chromosome aberration test in Chinese hamster lung （CHL） fibroblasts, and an in vivo micronucleus test in rat bone marrow cells. In the bacterial reverse mutation assay, we observed no increases in the number of revertant colonies at any concentrations of hyperoside regardless of metabolic activation （S9） in all tester strains （TA97, TA98, TA100 and TA102） compared to the vehicle control （P0.05）. Hyperoside did not cause significant structural aberration in CHL cells in the presence or absence of S9 （P0.05）. The micronuclei rates of mice bone marrow cell in all groups showed no significant difference when compared with the negative control （P0.05）. In summary, hyperoside showed no genotoxicity in our experimental conditions.研究黄蜀葵花提取物金丝桃苷的急性毒性和遗传毒性,对其安全性进行评价。急性毒性试验中,选用健康BALB/c小鼠40只,雌雄各半,灌胃给药(5000mg/kg),连续观察14天,记录中毒和死亡情况,测定小鼠的半数致死量(LD50)。用目前新药遗传毒性评价中推荐使用的3种试验方法,营养缺陷型鼠伤寒沙门氏菌回复突变试验(Ames试验),中国仓鼠肺成纤维细胞(CHL)染色体畸变试验和小鼠骨髓微核试验研究金丝桃苷的遗传毒性。在急性毒性试验中,所有实验动物都存活,且行为活泼,未见明显异常。Ames试验中,金丝桃苷在加或不加肝微粒体酶(S9)时均未见引起TA97、TA98、TAl00和TAl02试验菌株基因突变(P>0.05)。体外CHL细胞染色体畸变试验中,金丝桃苷在加或不加S9时均未引起CHL细胞的染色体畸变(P>0.05)。小鼠微核试验中,金丝桃苷各剂量组小鼠骨髓多染红细胞微核率与阴性对照组相比,差异无统计学意义(P>0.05)。在本实验条件下,金丝桃苷对于BALB/c小鼠的LD50大于5000mg/kg,金丝桃苷没有遗传毒性。

关 键 词：HYPEROSIDE Acute toxicity GENOTOXICITY 

分 类 号：R285[医药卫生—中药学]