Quadros Gomes Antonio Rafael, da Rocha Galucio Natasha Costa, de Albuquerque Kelly Cristina Oliveira, Brígido Heliton Patrick Cordovil, Varela Everton Luiz Pompeu, Castro Ana Laura Gadelha, Vale Valdicley Vieira, Bahia Marcelo Oliveira, Rodriguez Burbano Rommel Mario, de Molfeta Fábio Alberto, Carneiro Liliane Almeida, Percario Sandro, Dolabela Maria Fâni
Postgraduate Program in Pharmaceutical Innovation, Federal University of Pará, Av. Augusto Corrêa, 1, Guamá, 66075-110, Belém, PA, Brazil.
Postgraduate Program in Genetics and Molecular Biology, Federal University of Pará, Av. Augusto Corrêa, 1, Guamá, 66075-110, Belém, PA, Brazil.
Toxicol Rep. 2021 Jul 31;8:1480-1487. doi: 10.1016/j.toxrep.2021.07.015. eCollection 2021.
has been shown to be a promising medicinal plant, and its activity has been associated with naphthoquinones. The present study aimed at evaluating the cytotoxicity, genotoxicity, and oral toxicity of the ethanol extract (EEEp), dichloromethane fraction (FDMEp) of , and isoeleutherin. For the cytotoxicity evaluation, the viability test (MTT) was used. Genotoxicity was accessed through the Comet assay (alkaline version), acute and subacute oral toxicities were also evaluated. The antioxidant capacity of the samples in the wells where the cells were treated with was evaluated. Furthermore, the participation of caspase-8 in the possible mechanism of action of isoeleutherin, eleutherin, and eleutherol was also investigated through a docking study. FDMEp and isoeleutherin were cytotoxic, with higher rates of DNA fragmentation observed for FDMEp and isoeleutherin, and all samples displayed higher antioxidant potential than the control. In the acute oral toxicity test, EEEp, FDMEp, and isoeleutherin did not cause significant clinical changes. In the subacute toxicity assay, EEEp and FDMEp also did not cause clinical, hematological, or biochemical changes. The three compounds bound similarly to caspase-8. Despite the results of cytotoxicity, studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8.
已被证明是一种有前景的药用植物，其活性与萘醌有关。本研究旨在评估乙醇提取物（EEEp）、二氯甲烷馏分（FDMEp）和异刺五加素的细胞毒性、遗传毒性和口服毒性。对于细胞毒性评估，使用了活力测试（MTT）。通过彗星试验（碱性版本）评估遗传毒性，还评估了急性和亚急性口服毒性。评估了用样品处理细胞的孔中样品的抗氧化能力。此外，还通过对接研究调查了半胱天冬酶 - 8在异刺五加素、刺五加素和刺五加醇可能的作用机制中的参与情况。FDMEp和异刺五加素具有细胞毒性，FDMEp和异刺五加素观察到更高的DNA片段化率，并且所有样品显示出比对照更高的抗氧化潜力。在急性口服毒性试验中，EEEp、FDMEp和异刺五加素未引起明显的临床变化。在亚急性毒性试验中，EEEp和FDMEp也未引起临床、血液学或生化变化。这三种化合物与半胱天冬酶 - 8的结合方式相似。尽管有细胞毒性结果，但研究表明使用EEEp似乎是安全的，细胞死亡可能涉及其与半胱天冬酶 - 8的结合。
