Evidence map›Paper›PMID 41693482›Full record

ArticleBiomolecules & biomedicine2026

Digoxin attenuates LPS-induced acute lung injury in mice via NF-κB and HIF-1α inhibition.

Abdulaziz M Alzahrani, Mai A Alim A Sattar Ahmad, Wafaa S Ramadan, Huda M Alkreathy

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Article in Biomolecules & biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Abdulaziz M AlzahraniDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutical Care, King Abdulaziz Hospital, Makkah, Saudi Arabia.
Mai A Alim A Sattar AhmadDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Wafaa S RamadanDepartment of Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Huda M AlkreathyDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Acute lung injury (ALI), which can progress to the highly lethal acute respiratory distress syndrome (ARDS), remains a condition with limited pharmacological interventions, highlighting the urgent need for mechanism-informed repurposing strategies. Given the reported inhibitory effects of digoxin on nuclear factor kappa B (NF-κB)-mediated inflammation, we assessed its prophylactic and therapeutic efficacy in a murine model of lipopolysaccharide (LPS)-induced ALI. Sixty-six adult male BALB/c mice were divided into control and LPS-challenged groups. The LPS group (5 mg/kg, intratracheal) was assigned to either prophylactic regimens (daily saline, dexamethasone 5 mg/kg, or digoxin 1 mg/kg, administered intraperitoneally for 5 days prior to LPS) or therapeutic regimens (same interventions initiated 12 h post-LPS for 3 days). At the study endpoint, pulmonary edema (wet-to-dry ratio) and lung injury pathways were analyzed in lung homogenates, including tumor necrosis factor-alpha (TNF-α), IL-6, myeloperoxidase (MPO), malondialdehyde (MDA), NF-κB (p65) DNA-binding activity, C-X-C motif chemokine ligand 2/macrophage inflammatory protein-2 (CXCL2/MIP-2), and hypoxia-inducible factor-1 alpha (HIF-1α), alongside histopathological evaluations. Digoxin significantly reduced pulmonary edema in the therapeutic group (p = 0.02) and decreased TNF-α levels (p = 0.014), while robustly suppressing IL-6 and MDA in both prophylactic and therapeutic settings (each p < 0.001). Moreover, digoxin lowered MPO levels prophylactically (p = 0.007) and therapeutically (p = 0.014). It also strongly inhibited NF-κB activation, reducing CXCL2/MIP-2, while decreasing HIF-1α in both regimens (each p < 0.001). Histological analysis corroborated these findings, revealing improved alveolar architecture and reduced inflammatory injury. In conclusion, digoxin exhibits potent immunomodulatory activity in experimental ALI, warranting further translational research focused on dose optimization and safety profiling.

Indexed as

Acute Lung InjuryDigoxinHypoxia-Inducible Factor 1, alpha SubunitNF-kappa BAnimalsDisease Models, AnimalLipopolysaccharidesLungMaleMiceMice, Inbred BALB CPeroxidasePulmonary EdemaDigoxinHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitLipopolysaccharidesNF-kappa BPeroxidase

Identifiers

PMID41693482
PMCPMC13170723

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.