Digoxin Derivative BD-8 Attenuates Oxidative Stress and Neuroinflammation in an LPS-Induced Experimental Model.

Authors

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

Published in

Cell biochemistry and biophysics. Jun 25, 2026. Epub Jun 25, 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.

PMID:
42348110
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.