Work

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

Year: 2026

Type: article

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.

Source: Cell Biochemistry and Biophysics

DOI: 10.1007/s12013-026-02108-x