Journal Article
Digoxin Derivative BD-8 Attenuates Oxidative Stress and Neuroinflammation in an LPS-Induced Experimental Model
Vitória Karolina Brandão Souza; Davi Azevedo Ferreira; Antônio Pereira Ribeiro Arantes; Elton de Sá Figueiredo; Millena Ferreira Rodrigues Fonseca; Pâmela Yasmin de Oliveira Ferreira; Martina Raissa Ribeiro; Paulo César Ghedini; Andreza Amália de Freitas Ribeiro; José Augusto Ferreira Perez Villar; Maira de Castro Lima; Israel José Pereira Garcia; Hérica L Santos; Cristoforo Scavone; Sandra Rodrigues Mascarenhas; Jacqueline Alves Leite
Cell Biochemistry and Biophysics · 2026
Abstract
Chronic neuroinflammation contributes to neuronal damage through oxidative stress and inflammatory mediators, highlighting the need for novel therapeutic strategies. This study evaluated the cytotoxicity and neuroprotective effects of BD-8, a digoxin-derived cardiosteroid, in vitro and in vivo. BD-8 showed lower cytotoxicity than digoxin, with CC₅₀ values of 7.4 µM in SH-SY5Y cells and 8.5 µM in BV-2 cells, while digoxin presented a CC₅₀ of 33 nM in SH-SY5Y cells. In vivo, BD-8 did not alter cardiac, hepatic, or renal biochemical markers, supporting its systemic safety profile. In the open-field test, BD-8 prevented LPS-induced locomotor impairment, significantly increasing total crossings at 0.56 mg/kg (62.07 ± 3.269; P < 0.05) and 1.12 mg/kg (66.31 ± 5.282; P < 0.001) compared to the LPS group. BD-8 also reduced lipid peroxidation levels in the cortex at 0.56 mg/kg (14.38 ± 0.5568; P < 0.001) and 1.12 mg/kg (13.94 ± 0.8372; P < 0.001), and in the hippocampus at 1.12 mg/kg (14.04 ± 0.5223; P < 0.001). Additionally, BD-8 modulated antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), in both the cortex and hippocampus and reduced IL-6 levels in these brain regions without altering BDNF (Brain Derived Neurotrophic Factor) levels. These findings support BD-8 as a promising candidate for neuroinflammatory disorders.