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口服药用植物引起的肾毒性:以雅甘为例。

Renal toxicity caused by oral use of medicinal plants: the yacon example.

机构信息

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.

出版信息

J Ethnopharmacol. 2011 Jan 27;133(2):434-41. doi: 10.1016/j.jep.2010.10.019. Epub 2010 Oct 15.

Abstract

AIM OF THE STUDY

Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs).

MATERIALS AND METHODS

The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days.

RESULTS

The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys.

CONCLUSIONS

The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic compounds in the leaves of the yacon. Based on our results, we do not recommend the oral use of yacon leaves to treat diabetes.

摘要

研究目的

雅甘[Smallanthus sonchifolius(Poepp。& Endl。)H. Robinson,菊科]是一种安第斯物种,在世界各地的几个国家,包括巴西,传统上被用作抗糖尿病草药。它的降血糖作用最近在正常和糖尿病大鼠中得到了证实。然而,关于长期口服雅甘叶提取物的安全性的研究还很缺乏。因此,进行这项工作是为了评估三种雅甘叶提取物的重复剂量毒性:作为茶浸液制备的水提取物(AE);富含倍半萜内酯(STLs)的叶冲洗提取物(LRE);一种无刚毛的叶极性提取物,或极性提取物(PE),它缺乏 STLs,但富含绿原酸(CGAs)。

材料和方法

通过 IR 光谱和 HPLC-UV-DAD 分析以及与标准化合物的比较,确认了每种提取物中的主要化合物类别。在 Wistar 大鼠中进行了为期 90 天的重复剂量毒性研究,评估了每种提取物的毒性。

结果

PE 富含 CGAs,但我们没有检测到任何 STLs。AE 和 LRE 显示出 STLs 的存在。极性提取物引起了一些生化参数的改变,但动物没有表现出行为毒性或器官严重损伤的迹象。用 AE(10、50 和 100mg/kg)和 LRE(10 和 100mg/kg)处理的大鼠血液中的特定生化参数(肌酐 7.0mg/dL、血糖 212.0mg/dL、白蛋白 2.8g/dL)的改变表明肾脏损伤,这通过肾脏的组织学分析得到了证实。

结论

长期口服 AE 后,血糖水平升高与肾脏损伤有关。这一观察结果表明,在早期研究中治疗 30 天后观察到的降血糖作用是可逆的,可能是雅甘毒性引起的肾脏损伤所致。由于在 AE 和 LRE 中都检测到 STLs,因此有强有力的证据表明这些萜类化合物是雅甘叶的主要毒性化合物。基于我们的结果,我们不建议口服雅甘叶来治疗糖尿病。

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