Araújo Marcela Carolina de Paula Michel, Barcellos Neila Márcia Silva, Vieira Paula Melo de Abreu, Gouveia Thiago Magalhães, Guerra Martha Oliveira, Peters Vera Maria, Saúde-Guimarães Dênia Antunes
Laboratory of Medicinal Plants, School of Pharmacy, Federal University of Ouro Preto,, Minas Gerais state, Brazil.
Laboratory of Experimental Pharmacology, School of Pharmacy, Federal University of Ouro Preto, Minas Gerais state, Brazil.
J Ethnopharmacol. 2017 Apr 6;201:17-25. doi: 10.1016/j.jep.2017.02.043. Epub 2017 Feb 28.
Campomanesia velutina leaves and branches infusions are used in Brazilian folk medicine to treat diarrhea and to ameliorate intestinal cramps, respectively.
Carry out the acute and sub chronic pre-clinical evaluation and thus assess the safety and toxicological potential of the specie.
In vivo toxicity was evaluated by acute and sub chronic toxicity assays conducted according to the guidelines of the Brazilian Agency of National Health Surveillance (Agência Nacional de Vigilância Sanitária - ANVISA). For acute toxicity evaluation, a single dose of aqueous extracts from the leaves (AEL) and branches (AEB) of Campomanesia velutina were orally administered to mice at doses of 300, 600 and 1200mg/kg. Then, the animals were observed for 14 days. In the sub chronic study, the extracts were orally administered to mice for 14 days at doses of 300, 600 and 1200mg/kg. To assess the toxicological effects, animals were closely observed on general behavior, clinical signs of toxicity, body weight, food and water intake. At the end of the experiment, it was performed biochemical and hematological evaluations, as well as histopathological analysis from the following organs: brain, heart, lungs, liver, stomach, small intestine (section) and left kidney. Preliminary phytochemical analysis was performed using thin layer chromatography (TLC) and colorimetric pharmacognostic tests.
In oral acute assay, treatment with AEB at the major dose (1200mg/kg) caused diarrhea, abdominal cramps and tremors in females. These effects were reversed at 4th hour. Normochromic normocytic anemia was observed in males treated with AEL 300mg/kg and AEB 600 and 1200mg/kg as well as in females treated with AEB 300 and 1200mg/kg. The kidney of all treated animals showed moderate inflammation and a few hemorrhagic points. In sub chronic assay, treatment with AEL 600mg/kg, AEL 1200mg/kg and AEB 1200mg/kg caused hyper excitability in females that was not reversed. Treatments also had impact on weight gain and the relative weight of males' brain was increased on group treated with AEL 300mg/kg, AEB 300 and AEB 1200mg/kg. Although changes in hematological parameters were not observed, serum creatinine levels were significantly higher in males treated with AEB 300mg/kg. Besides, the heart of all treated animals showed intense hyperemia. Preliminary phytochemical analysis revealed the presence of flavonoids, tannins and phenolic compounds.
Toxicity signs were mainly observed after treatment with AEL and AEB at the two highest tested doses (600 and 1200mg/kg), suggesting that the extracts are relatively safe at its effective dose (300mg/kg). However, alterations on hematological and biochemical parameters and on the kidney and heart of the animals were not closely related with the dose, implying caution on its use.
绒毛番樱桃的叶和枝的浸剂在巴西民间医学中分别用于治疗腹泻和缓解肠道痉挛。
进行急性和亚慢性临床前评估，从而评估该物种的安全性和毒理学潜力。
根据巴西国家卫生监督局（Agência Nacional de Vigilância Sanitária - ANVISA）的指南，通过急性和亚慢性毒性试验评估体内毒性。对于急性毒性评估，将绒毛番樱桃叶（AEL）和枝（AEB）的水提取物以300、600和1200mg/kg的剂量口服给予小鼠。然后，观察动物14天。在亚慢性研究中，将提取物以300、600和1200mg/kg的剂量口服给予小鼠14天。为评估毒理学效应，密切观察动物的一般行为、毒性临床体征、体重、食物和水摄入量。实验结束时，进行生化和血液学评估，以及对以下器官进行组织病理学分析：脑、心脏、肺、肝脏、胃、小肠（切片）和左肾。使用薄层色谱法（TLC）和比色生药学试验进行初步植物化学分析。
在口服急性试验中，高剂量（1200mg/kg）的AEB处理导致雌性小鼠腹泻、腹部痉挛和震颤。这些效应在第4小时逆转。在接受300mg/kg AEL、600和1200mg/kg AEB处理的雄性小鼠以及接受300和1200mg/kg AEB处理的雌性小鼠中观察到正色素正细胞性贫血。所有处理动物的肾脏均显示中度炎症和一些出血点。在亚慢性试验中，600mg/kg AEL、1200mg/kg AEL和1200mg/kg AEB处理导致雌性小鼠过度兴奋且未逆转。处理还对体重增加有影响，在接受300mg/kg AEL、300mg/kg AEB和1200mg/kg AEB处理的组中，雄性小鼠的脑相对重量增加。尽管未观察到血液学参数变化，但接受300mg/kg AEB处理的雄性小鼠血清肌酐水平显著升高。此外，所有处理动物的心脏均显示强烈充血。初步植物化学分析显示存在黄酮类、单宁和酚类化合物。
主要在以两个最高测试剂量（600和1200mg/kg）的AEL和AEB处理后观察到毒性体征，表明提取物在其有效剂量（30mg/kg）下相对安全。然而，动物血液学和生化参数以及肾脏和心脏的改变与剂量没有密切关系，意味着使用时需谨慎。
