小飞蓬黄酮的安全性毒理学研究

Study on Toxicity and Safety of Flavonoid Components from Xiaofeipeng(Erigeron canadensis)

目的研究小飞蓬黄酮组分的急性毒性、遗传毒性及长期毒性,以评估其食用安全性。方法采用高效液相色谱法及分光光度法分别测定10批小飞蓬黄酮组分(受试物)中黄酮成分及总黄酮含量;以最大给药量1.36 g/kg·BW给予小鼠,24 h内灌胃给药1次,连续观察14 d;遗传毒性实验(Ames实验、小鼠骨髓细胞微核实验、小鼠精子畸形实验);用高、中、低剂量[167、333、667 mg/(kg·BW)]的小飞蓬黄酮灌胃给予大鼠,连续给药13周,停药恢复2周。结果小飞蓬黄酮组分(受试物)总黄酮含量在75%以上,所含有的黄酮成分飞蓬黄酮苷、槲皮素、藤黄菌素含量分别为3.33%、7.88%、6.68%。小鼠经口最大耐受剂量(MTD)均>1.36 g/(kg·BW),急性毒性试验未见明显中毒症状。3项遗传毒性试验结果均为阴性,表明该受试物无致突变作用。在大鼠13周喂养试验中,实验动物均生长发育良好,体质量、摄食量、饮水量、血液学、血液生化学、脏器系数及病理组织学相关指标均未见异常变化。结论在本实验条件下,小飞蓬黄酮对受试动物无明显毒性反应,安全剂量范围大,在有效剂量下,长期用药安全。

Objective To study the acute toxicity, genetic toxicity and chronic toxicity of flavonoid components from Xiaofeipeng(Erigeron canadensis), so as to assess its safety. Method HPLC and UV were used to determine the contents of flavonoid and total flavonoids in the flavonoid components(test substance) of 10 batches of Xiaofeipeng(Erigeron canadensis). Mice were administered the drug with a maximal dose[1.36 g/(kg·BW)]. The drug was given by gavage once in 24 hours for 14 days. Genotoxicity test(Ames test, Microkernel test and Sperm malformation test) was carried out. The rats were divided into high, middle and low groups, receiving 167 mg/(kg·BW), 333 mg/(kg·BW) and 333 mg/(kg·BW) flavonoid components, lasting for 3 weeks. Continuous administration was lasted for 13 weeks and the rats recovered after 2 weeks of withdrawal. Results The content of total flavonoids in the flavonoid components(test substance) of Xiaofeipeng(Erigeron canadensis) was more than 75%. The contents of erigeroside, quercetin and luteolin in the flavonoid components(test substance) of Xiaofeipeng(Erigeron canadensis) were 3.33%, 7.88% and 6.68%,respectively. Maximally tolerated dose(MTD) of the flavonoid components was more than 1.36 g/(kg·BW) in acute toxicity test and there were no obvious symptoms of poisoning in acute toxicity test. Ames test, microkernel test and sperm malformation test showed the sample was safe without mutagenesis. A negative result was obtained in genotoxicity test. In the 13 weeks feeding experiment of rats, the growth and development of the rats were good, and the body weight, food intake, water intake, hematology, biochemistry, organ coefficient and histopathology related indexes were not abnormal. Conclusion In the conditions of this experiment, flavonoid components of Xiaofeipeng(Erigeron canadensis) have no obvious toxic reaction to the tested animals. Flavonoid components from Xiaofeipeng(Erigeron canadensis) have a large range of safe doses, and long-term medication is safe at effective doses.