醇沉对益母草水提物的小鼠急性毒性及毒靶器官的影响

摘要/Abstract

摘要： 目的比较醇沉工艺对益母草水提物急性毒性的影响和毒性靶器官损伤程度的差异。方法运用紫外分光光度法测定不同样品中益母草总生物碱的含量,急性毒性实验法对其急性毒性进行比较,记录其毒性症状、累积死亡数和小鼠体重变化,并于药后7天,取血,检测血液生化指标,取肝脏、肾脏称重,并计算脏器系数和进行病理组织学观察。结果益母草水提物和水提醇沉物中总生物碱的含量分别为0.50%和0.37%。益母草水提物和水提醇沉物的MTD分别为88.0 g·kg-1和187.5 g·kg-1,相当于临床70 kg人日用量的205.3、437.5倍,水提组和水提醇沉组均有1只小鼠死亡。益母草水提和水提醇沉物均可导致小鼠BUN、Cr水平明显升高（P<0.001）,肾脏系数明显升高（P<0.01）;水提物与水提醇沉物进行比较,水提组小鼠BUN、Cr水平升高（P>0.05）,肾脏系数明显升高（P<0.01）;益母草水提可导致小鼠ALT、AST水平升高（P<0.01）,水提醇沉物可导致小鼠AST水平升高（P<0.01）,肝脏系数升高（P>0.05）;水提物与水提醇沉物进行比较,水提组小鼠ALT、AST水平和肝脏系数升高（P>0.05）。肝、肾病理表明,小鼠肝、肾组织未见明显病理改变。结论急性毒性试验显示益母草提取物的毒性靶器官主要为肾脏、肝脏,表现为BUN、Cr水平的显著增高和ALT、AST水平的增高和肝、肾脏系数的增加,其中肾脏毒性重于肝脏,益母草水提物毒性大于水提醇沉物,结合益母草水提物和水提醇沉物的含量分析数据,提示益母草提取物的毒性与总生物碱的含量呈现一定相关性,醇沉工艺后总生物碱的含量和毒性显著降低,可能与醇沉除去水溶性杂质有关,具体的物质基础还有待进一步研究。

关键词: 益母草, 醇沉, 水提物, 急性毒性, 靶器官

Abstract: Objective To study the influence of alcohol precipitating on water extracts from Herba Leonuri for acute toxicity, the damage degree of toxicity target organs in mice. Method UV spectrophotometry was used to measure the content of total alkaloids, the method of acute toxicity was used to compare the difference of acute toxicity between different water extracting processes. The toxic symptoms, cumulative mortality, weight changes of mice were recorded. Seven days after administration, blood was taken, the contents of serum biochemical indicators were detected while the liver, kidney were taken for organ coefficient. Results The contents of total alkaloids of Herba Leonuri in water extracts, alcohol precipitated water extracts were separately0.50%, 0.27%. MTD of water extracts, alcohol precipitated water extracts were88.0g·kg-1, 187.5g·kg-1, which were respectively equal to205.3, 437.5times of70kg human daily dried medicinal herb doses. There was one mouse died in each group. Compared with normal control group, the water extracts, alcohol precipitated water extracts from Herba Leonuri all could lead to significant increase of mice's BUN, Cr levels, kidney coefficient increased significantly. Compared with alcohol precipitated water extracts, the BUN, Cr levels of water extract group increased, kidney coefficient increased significantly. Compared with normal control group, the ALT, AST levels of water extract group increased. Alcohol precipitated water extracts could lead to AST level increasing, liver coefficient increased. Compare with alcohol precipitated water extracts, the ALT, AST, liver coefficient of water extract increased. Liver, kidney pathology showed that there were no obvious pathological changes in the liver, kidney tissues of mice. Conclusion Acute toxicity test showed that the toxicity target organs of Herba Leonuri were mainly kidney, liver. It proved that BUN, Cr levels significantly increased, ALT, AST levels increased, liver, kidney coefficients increased. The toxicity of kidney was higher than that of liver, the toxicity of water extract was higher than alcohol precipitated water extract. Combined with assay data of water extract, alcohol precipitated water extract from Herba Leonuri, it is suggested that the toxicity of Herba Leonuri's extracts, total alkaloids content showed a certain correlation. The toxicity, content of total alkaloids significantly decreased through alcohol precipitating process. Maybe alcohol precipitating process removed water soluble impurities, but the material base is still to be further studied

Key words: Herba Leonuri, alcohol precipitating, water extract, acute toxicity, target organ

中图分类号:

R992

孙晓倩,黄娜娜,尹立顺,李晓宇,吕莉莉,赵红,孙蓉,. 醇沉对益母草水提物的小鼠急性毒性及毒靶器官的影响[J]. 中国药物警戒, 2015, 12(12): 717-721.

SUN Xiao-qian, HUANG Na-na, YIN Li-shun, LI Xiao-yu, LV Li-li, ZHAO Hong, SUN Rong. Influence of Alcohol Precipitating on Acute Toxicity and Toxicity Target Organs of Water Extracts from Herba Leonuri in Mice [J]. Chinese Journal of Pharmacovigilance, 2015, 12(12): 717-721.

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