Toxicity evaluation of Eleutherine plicata Herb. extracts and possible cell death mechanism

• Published in: Toxicology reports 2021-01, Vol.8, p.1480-1487
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Caspase-8; Eleutherin; Eleutherine plicata; Eleutherol; Isoeleutherin; Regular; Toxicity
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2021.07.015

[Display omitted] •Ethanol extract of Eleutherine plicata showed low in vitro and in vivo cytotoxic potential.•The dichloromethane fraction was cytotoxic to HepG2 and caused DNA. However, no toxicity was observed in vivo.•Isoeleutherin caused DNA damage by the comet method and activated caspase-8 in the in silico study. 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.