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延胡索乙素,一种源于紫堇科紫堇属植物东北延胡索块茎的生物碱,其抗血栓、抗凝及毒性研究。

The antithrombotic, anticoagulant activity and toxicity research of ambinine, an alkaloid from the tuber of Corydalis ambigua var. amurensis.

机构信息

Development and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Materia, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

Development and Utilization Key Laboratory of Northeast Plant Materials, School of Traditional Chinese Materia, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

出版信息

Regul Toxicol Pharmacol. 2018 Jun;95:175-181. doi: 10.1016/j.yrtph.2018.03.004. Epub 2018 Mar 7.

Abstract

Ambinine, the major alkaloid of the tuber of Corydalis ambigua var. amurensis, has protective effects on HC myocardial cells. In the present paper, we observed that ambinine demonstrates activities of both anticoagulation and thrombolysis in vitro by significantly degrading the blood clot and delaying the plasma recalcification time (PRT) in a dose-dependent manner (0.5-2 mg/mL). We further studied its safety profile of acute and subacute toxicity by repeated-dose intravenous injection. The median lethal dosage (LD) of mice given by oral and intravenous administration of ambinine were approximate 800, 41.60 mg/kg, respectively. The acute toxicity research results suggested that compared with an intravenous administration, the oral route is safer to administer ambinine as the promising lead compound for thrombosis. In subacute toxicity research, when mice were given ambinine at doses of 1.40 and 2.10 mg/kg for 7 days by injection, significant alteration of the relative kidney weight, the relative liver weight and serum biochemistry parameters and marked histopathological changes of them were found.

摘要

延胡索乙素是紫堇属植物东北延胡索块茎中的主要生物碱,具有保护人心肌细胞 HC 的作用。本文研究发现延胡索乙素在体外具有抗凝和溶栓活性,能显著降解血凝块,且呈剂量依赖性延长血浆复钙时间(PRT)(0.5-2mg/mL)。进一步通过重复静脉注射给药研究其急性和亚急性毒性的安全性特征。灌胃和静脉给予延胡索乙素的小鼠的半数致死剂量(LD)分别约为 800、41.60mg/kg。急性毒性研究结果表明,与静脉给药相比,口服途径给予延胡索乙素更为安全,有望成为治疗血栓的先导化合物。在亚急性毒性研究中,当小鼠以 1.40 和 2.10mg/kg 剂量经注射给予延胡索乙素 7 天时,发现相对肾重、相对肝重以及血清生化参数发生显著改变,且它们出现明显的组织病理学变化。

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