Toxicity evaluation of Eleutherine plicata Herb. extracts and possible cell death mechanism
Antônio Rafael Quadros Gomes, Natasha Costa da Rocha Galucio, Kelly Cristina Oliveira de Albuquerque, Heliton Patrick Cordovil Brígido, Everton Luiz Pompeu Varela, Ana Laura Gadelha Castro, Valdicley Vieira Vale, Marcelo de Oliveira Bahia, Rommel Mário Rodríguez Burbano, Fábio Alberto de Molfeta, Liliane Almeida Carneiro, Sandro Percário, Maria Fâni Dolabela
Abstract
Eleutherine plicata 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 E. plicata, 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 E. plicata 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, in vitro studies demonstrated that the use of EEEp appears to be safe and cell death may involve its binding to caspase-8.