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双羽叶狄氏木(Dilodendron bipinnatum Radlk.)水乙醇提取物的毒理学评价

Toxicological evaluation of the hydroethanolic extract of Dilodendron bipinnatum Radlk.

作者信息

de Azevedo Neta Mahon Clarisse Pinto Coelho, Colodel Edson Moleta, Balogun Sikiru Olaitan, de Oliveira Ruberlei Godinho, de Oliveira Martins Domingos Tabajara

机构信息

Departament of Basic Sciences in Health, Faculty of Medicine, Federal University of Mato Grosso (UFMT) 78060-900, Cuiabá, MT, Brazil.

Laboratory of Veterinary Pathology, Faculty of Agronomy and Veterinary Medicine, Federal University of Mato Grosso (UFMT) 78060-900, Cuiabá, MT, Brazil.

出版信息

J Ethnopharmacol. 2014 Aug 8;155(1):665-71. doi: 10.1016/j.jep.2014.06.018. Epub 2014 Jun 13.

DOI:10.1016/j.jep.2014.06.018
PMID:24933228
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Dilodendron bipinnatum Radlk., Sapindaceae, is popularly known as 'mulher-pobre'. Its stem bark macerate or decoction is popularly used mainly to treat uterine inflammation and bone fractures. Acute oral and subchronic toxicities of the hydroethanolic extract of Dilodendron bipinnatum (HEDb) were investigated as well as the classes of phytochemical present in the extract.

MATERIALS AND METHODS

Acute toxicity of HEDb was investigated by hippocratic screening in Swiss mice, cytotoxicity and potential genotoxic effect were evaluated with micronucleus test in the CHO-k1cells. Subchronic oral toxicity of HEDb was assessed in Wistar rats with graded doses of HEDb repeatedly administered for 30 days, in order to evaluate the behavioral changes, weight gain, water and feed consumption, urine and feces excretion, hematological and biochemical parameters and histopathological examinations of vital organs.

RESULTS

In hippocratic screening doses up to 5000 mg/kg p.o. did not cause any changes in female mice, while signs of reduction in motility, increased respiratory rate and tail erection were observed in male mice but were all reversed within an hour. In cytotoxicity assay, IC50 was 118±1.55 µg/mL in CHO-k1 cells. Micronucleus test demonstrated that the plant extract is non-genotoxic. In subchronic toxicity studies, minor change was observed as an increase in the urine output in the last 18 days of treatment with 500 mg/kg of HEDb, while other parameters remained unchanged. All alterations observed were discrete and minor in nature and were not accompanied by any relevant clinical signs or any toxicologically significant biochemical, hematological and histopathological changes. Preliminary phytochemical analysis revealed the presence of aurones, chalcones, coumarins, flavonones, flavononoids, phenols, and saponins.

CONCLUSION

The results demonstrate high safety profile of HEDb in both experimental animals and cell models assays. However, there may be risk of hepatotoxicity in the use of the extract at high doses for a prolonged period.

摘要

民族药理学相关性

无患子科的二回羽状复叶无患子,俗称“穷女人”。其茎皮浸剂或煎剂主要用于治疗子宫炎症和骨折。研究了二回羽状复叶无患子水乙醇提取物(HEDb)的急性口服毒性和亚慢性毒性以及提取物中存在的植物化学类别。

材料与方法

通过希波克拉底筛选法在瑞士小鼠中研究HEDb的急性毒性,用CHO - k1细胞微核试验评估细胞毒性和潜在的遗传毒性作用。在Wistar大鼠中评估HEDb的亚慢性口服毒性,以分级剂量反复给药30天,以评估行为变化、体重增加、水和饲料消耗、尿液和粪便排泄、血液学和生化参数以及重要器官的组织病理学检查。

结果

在希波克拉底筛选中,口服剂量高达5000 mg/kg对雌性小鼠未引起任何变化,而雄性小鼠出现运动减少、呼吸频率增加和尾巴竖起的迹象,但在一小时内全部恢复。在细胞毒性试验中,CHO - k1细胞中的IC50为118±1.55 µg/mL。微核试验表明该植物提取物无遗传毒性。在亚慢性毒性研究中,在用500 mg/kg的HEDb治疗的最后18天观察到尿量增加的轻微变化,而其他参数保持不变。观察到的所有改变本质上都是离散和轻微的,并且没有伴随任何相关的临床体征或任何毒理学上显著的生化、血液学和组织病理学变化。初步植物化学分析显示存在橙酮、查耳酮、香豆素、黄酮醇、黄酮类化合物、酚类和皂苷。

结论

结果表明HEDb在实验动物和细胞模型试验中具有高安全性。然而,长期高剂量使用该提取物可能存在肝毒性风险。

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