中国药物警戒 ›› 2015, Vol. 12 ›› Issue (12): 705-710.

• 益母草提取方式与毒性研究专栏 •    下一篇

不同提取方式对益母草小鼠急性毒性及毒靶器官的影响

吕莉莉1, 赵红2, 李世民1, 黄娜娜3, 孙晓倩3, 李晓宇1, 孙蓉1*   

  1. 1山东省中医药研究院,山东 济南 250014;
    2中国人民解放军海军总医院,北京 100048;
    3山东中医药大学,山东 济南 250355
  • 收稿日期:2016-02-02 修回日期:2016-02-02 出版日期:2015-12-08 发布日期:2016-02-02
  • 通讯作者: 孙蓉,女,博士,研究员·博导,中药药理与毒理。E-mail:sunrong107@163.com
  • 作者简介:吕莉莉,女,副研究员,中药药理与毒理。
  • 基金资助:
    国家自然科学基金项目(81450021); 山东省自主创新和成果转化项目(2014ZZCX02104)

Influence of Different Extraction Methods on Acute Toxicity and Toxicity Target Organs of Herba Leonuri in Mice

LV Li-li1, ZHAO Hong2, LI Shi-min1, HUANG Na-na3, SUN Xiao-qian3, LI Xiao-yu1, SUN Rong1, *   

  1. 1Shandong Academy of Chinese Medicine, Shandong Ji'nan 250014, China;
    2PLA Navy General Hospital, Beijing 100048, China;
    3Shandong University of Traditional Chinese Medicine, Shandong Ji'nan 250355, China
  • Received:2016-02-02 Revised:2016-02-02 Online:2015-12-08 Published:2016-02-02

摘要: 目的比较益母草醇提和水提工艺样品对小鼠急性毒性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提取工艺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。结果益母草醇提和水提物中总生物碱的含量分别为0.82%和0.50%,益母草醇提物的LD50为118.68 g·kg-1,相当于临床70 kg人日用量的276.9倍;95%可信限分别为112.84~124.89 g·kg-1,相当于临床70 kg人日用量的263.3~291.4倍。益母草水提物的MTD为88.0 g·kg-1,相当于临床70 kg人日用量的205.3倍。益母草醇提和水提物均可导致小鼠BUN、Cr水平明显升高(P<0.001),肾脏系数明显升高,经统计学检验与正常对照组比较呈现不同程度的差异性;醇提物与水提物进行比较,醇提1~4组小鼠BUN、Cr水平升高(P>0.05),肾脏系数明显升高,经统计学检验,仅醇提1组呈现非常显著性差异;益母草醇提1~2组和水提物均可导致小鼠ALT、AST水平升高,经统计学检验与正常对照组比较呈现不同程度的差异性,醇提1组可导致肝脏系数升高,有非常显著性差异(P<0.01);醇提物与水提物比较,醇提1组的ALT水平和肝脏系数有非常显著性差异(P<0.01)。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,益母草醇提物毒性大于水提物,结合益母草醇提物和水提物的含量分析数据,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,有待于进一步深入探讨总生物碱与肾毒性的相关性。

关键词: 益母草, 水提物, 醇提物, 急性毒性

Abstract: ObjectiveTo study the influence of water and alcohol extracting process from Herba Leonuri on acute toxicity and the damage degree of toxicity target organs. MethodsUV spectrophotometry was used to measure the content of total alkaloids and the method of acute toxicity was used to compare the difference of acute toxicity between different extracting processes, and recording its toxic symptoms, cumulative mortality and weight change in mice. Seven days after administration, blood was taken and the contents of serum biochemical indicators were detected while the liver and kidney were taken for organ coefficient. ResultsThe contents of total alkaloids in alcohol extracts and water extracts from Herba Leonuri were separately 0.82% and 0.50%. The LD50 of alcohol extracts from Herba Leonuri is 118.68 g·kg-1,which is equal to 276.9 times of 70 kg human daily dried medicinal herb dose. The 95% confidence interval is 112.84~124.89 g·kg-1, which is equal to 263.3~291.4 times of 70 kg human daily dried medicinal herb dose. The MTD of water extracts form Herba Leonuri is 88.0 g·kg-1, which is equal to 205.3 times of 70 kg human daily dried medicinal herb dose. Alcohol extraction and water extraction from Herba Leonuri all could lead to significant increase (P<0.001) of mice's BUN and Cr levels. Kidney coefficient increased significantly, compared with normal control group, the statistical tests showed varying degree difference. Compared with water extract, the BUN and Cr levels in group 1~4 of alcohol extraction increased (P>0.05). Kidney coefficient increased significantly, and the statistical test showed that only group 1 of alcohol extraction had very significant difference. The group 1 and 2 of alcohol extraction and water extraction from Herba Leonuri showed increased ALT and AST. Compared with normal control group, the statistical tests showed the varying degree difference. Group 1 of alcohol extraction could lead to liver coefficient increase which showed very significant difference (P<0.01). Compared with water extract, the ALT level and liver coefficient of group 1 of alcohol extraction showed very significant difference(P<0.01). Liver and kidney pathology showed that there were no obvious pathological changes in liver and kidney tissues of mice. ConclusionAcute toxicity test showed that the toxicity target organs of Herba Leonuri were mainly kidney and liver. It proved that the BUN and Cr levels significantly increased, the ALT and AST levels increased, liver and kidney coefficients increased. The toxicity of kidney was higher than that of liver, and the toxicity of alcohol extract is higher than that of water extract. Combined with assay data of alcohol and water extracts from Herba Leonuri, it is suggested that the toxicity of Herba Leonuri's extracts and total alkaloids content showed a certain correlation, and we need to further explore the correlation of total alkaloids and renal toxicity.

Key words: Herba Leonuri, water extract, alcohol extract, acute toxicity

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