苍耳子炮制前后急性毒性及毒效成分含量差异研究

Comparative Analysis of Acute Toxicity and Content of Toxic and Active Components in Crude and Processed Xanthii Fructus

目的:研究苍耳子炮制前后对小鼠的急性毒性及主要毒性成分、药效成分的含量差异。方法:急性毒性实验采用小鼠灌胃给药测定其半数致死量(LD50)和最大耐受量(MTD),并通过组织病理切片观察其对小鼠肝、肾等脏器的损伤;采用高效液相色谱法比较苍耳子炮制前后2种水溶性苷类毒性成分和4种酚酸类有效成分的含量差异。结果:苍耳子的水煎剂和水煎剂醇沉沉淀,以及炒苍耳子的水煎剂和水煎剂醇沉沉淀的MTD分别为291.73 g生药/kg、405.75 g生药/kg、318.64 g生药/kg和480.77 g生药/kg。炮制前后苍耳子水煎剂醇沉上清的LD50分别为468.18 g生药/kg和573.48 g生药/kg。组织病理结果显示死亡小鼠多数脏器出现不同程度的充血,以肝、肺、胃和小肠最为明显。苍耳子炮制后,水煎剂和水煎剂醇沉上清液中的羧基苍术苷含量均显著降低(均P<0.01);炒苍耳子中咖啡酸和异绿原酸C的含量显著升高(均P<0.01)。结论:苍耳子炮制后毒性可显著降低,有效成分溶出增加。水煎剂醇沉上清液取自苍耳子的主要毒性部位。

Objective:To study the difference in acute toxicity in mice and the content of toxic and active components of Xanthii Fructus before and after stir-frying.Methods:In the acute toxicity experiment, mice were administered by gavage, and the median lethal dose(LD50) and the maximum tolerated dose(MTD) in mice were determined.The damage to the liver, kidney, and other organs of mice was observed by histopathological sections.The content of two water-soluble glycosides and four phenolic acids of crude and processed Xanthii Fructus was quantitatively determined by high-performance liquid chromatography(HPLC).Results:MTDs of water decoction and precipitate after alcohol precipitation of crude Xanthii Fructus and water decoction and precipitate after alcohol precipitation of processed Xanthii Fructus were 291.73,405.75,318.64,and 480.77 g/kg(calculated based on the crude drug),respectively.The LD50 values of supernatant after alcohol precipitation of crude and processed Xanthii Fructus were 468.18 and 573.48 g/kg(calculated based on the crude drug),respectively.Hyperemia of different degrees was observed in the pathological sections of the main organs of the dead mice, especially in the liver, lung, stomach, and small intestine.The content of carboxyatractyloside in the water decoction and supernatant after alcohol precipitation decreased after stir-frying(both P<0.01),and the content of caffeic acid and isochlorogenic acid C increased(both P<0.01).Conclusion:After stir-frying, the toxicity of Xanthii Fructus was significantly reduced and the dissolution of active components increased.The supernatant after alcohol precipitation of water decoction was the main toxic part of Xanthii Fructus.