94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1537720
This article is part of the Research Topic The Sodium Pump and Cardiotonic Steroids in Health and Disease View all articles
Evaluation of the Neuroprotective Potential of Benzylidene Digoxin 15 (BD-15) against Oxidative Stress in a Neuroinflammation Models Induced by Lipopolysaccharide (LPS) and on neuronal differentiation of hippocampal neural precursor cells
Provisionally accepted
Gilvânia AR Cordeiro 1* Jessica Alves Faria 1* Leticia Pavan Anjos 2* Israel JP Garcia 1* Eduarda Paula Ferreira Invernizzi Neves 3* Gustavo Frazão 1*
Hericles Mesquita Campos 3 Pâmela Yasmin de Oliveira Ferreira 3* Paulo César Ghedini 3* Elisa Mitiko Kawamoto 2* Maira Castro Lima 1* José Augusto FP Villar 1*
Ana Maria Marques Orellana 2
Leandro Barbosa 1
Cristoforo Scavone 2
Jacqueline Leite 3* Hérica Lima Santos 1*- 1 Universidade Federal de São João del-Rei, São João del Rei, Minas Gerais, Brazil
- 2 Pharmacology, University of São Paulo, São Paulo, São Paulo, Brazil
- 3 Universidade Federal de Goiás, Goiânia, Goiás, Brazil
Neuroinflammation, often driven by the overproduction of reactive oxygen species (ROS), plays a crucial role in the pathogenesis of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The susceptibility of the brain to oxidative stress is attributed to its high metabolic activity and limited antioxidant defense. This study aimed to evaluate the neuroprotective potential of Benzylidene Digoxin 15 (BD-15) following treatment and pretreatment in a lipopolysaccharide (LPS)induced neuroinflammation model. Additionally, we examined whether BD-15 enhances the generation of neurons from neural progenitor cells (NPCs).Male Wistar rats were used for acute treatment studies and divided into four groups: control (saline), BD-15 (100 µg/kg), LPS (250 µg/kg), and LPS + BD-15 (250 µg/kg + 100 µg/kg). Swiss albino mice were used for chronic pretreatment studies and divided into the following groups: control (saline), BD-15 (0.56 mg/kg), LPS (1 mg/kg), and LPS + BD-15 (1 mg/kg + 0.56 mg/kg). Behavioral changes were assessed using the open field test, and brain tissues were analyzed for oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), protein carbonylation, catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). To assess neurogenesis, primary NPC cultures derived from the hippocampus of newborn Wistar rats were used, which led to reduced locomotor activity and increased oxidative stress, particularly in the cortex, as indicated by elevated MDA levels and reduced GSH levels. BD-15 treatment reversed these effects, notably by restoring GSH levels and reducing protein carbonylation in the cerebellum. Chronic BD-15 treatment in Swiss mice improved oxidative stress markers including MDA, SOD, CAT, and GST. Furthermore, BD-15 exhibits neuroprotective properties by alleviating oxidative stress and motor dysfunction, suggesting its potential as a therapeutic agent for neuroinflammatory disorders. However, BD-15 did not affect NPC cell proliferation, indicating that this cardiotonic steroid did not alter the cell cycle of these progenitor cells.
Keywords: BD-15, Neuroinflammation, Cerebellum, Prefrontal Cortex, Sxidative stress, Hippocampal neurogenesis
Received: 04 Dec 2024; Accepted: 12 Feb 2025.
Copyright: © 2025 Cordeiro, Faria, Anjos, Garcia, Neves, Frazão, Campos, Ferreira, Ghedini, Kawamoto, Lima, Villar, Orellana, Barbosa, Scavone, Leite and Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Gilvânia AR Cordeiro, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Jessica Alves Faria, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Leticia Pavan Anjos, Pharmacology, University of São Paulo, São Paulo, 05508-000, São Paulo, Brazil
Israel JP Garcia, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Eduarda Paula Ferreira Invernizzi Neves, Universidade Federal de Goiás, Goiânia, 74001-970, Goiás, Brazil
Gustavo Frazão, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Pâmela Yasmin de Oliveira Ferreira, Universidade Federal de Goiás, Goiânia, 74001-970, Goiás, Brazil
Paulo César Ghedini, Universidade Federal de Goiás, Goiânia, 74001-970, Goiás, Brazil
Elisa Mitiko Kawamoto, Pharmacology, University of São Paulo, São Paulo, 05508-000, São Paulo, Brazil
Maira Castro Lima, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
José Augusto FP Villar, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Jacqueline Leite, Universidade Federal de Goiás, Goiânia, 74001-970, Goiás, Brazil
Hérica Lima Santos, Universidade Federal de São João del-Rei, São João del Rei, 36307-352, Minas Gerais, Brazil
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.