Daily Ards Research Analysis
Today's ARDS-related research highlights a preclinical repurposing study showing cilostazol mitigates LPS-induced acute lung injury in rats. The drug attenuated inflammatory signaling (NF-κB/TLR4/JAK-STAT3), reduced edema and cytokines, and improved respiratory parameters, supported by in silico multi-target docking.
Summary
Today's ARDS-related research highlights a preclinical repurposing study showing cilostazol mitigates LPS-induced acute lung injury in rats. The drug attenuated inflammatory signaling (NF-κB/TLR4/JAK-STAT3), reduced edema and cytokines, and improved respiratory parameters, supported by in silico multi-target docking.
Research Themes
- Drug repurposing for ALI/ARDS
- Inflammatory signaling modulation (NF-κB/TLR4/JAK-STAT3)
- Integrative in silico docking with in vivo validation
Selected Articles
1. Investigation of the protective effect of cilostazol on acute lung injury-mediated inflammation and in silico molecular modelling studies of inflammatory signalling pathway: a repurposing study.
In an LPS-induced rat ALI model, cilostazol bound multiple inflammatory proteins in silico and reduced oxidative stress, cytokines (IL-6, TNF-α), KL-6, LDH, MPO, CRP, NO, edema, vascular leakage, and inflammatory cell recruitment in vivo. It downregulated TNF-α, NF-κB, TLR4, and JAK/STAT3 mRNA and improved total lung capacity, supporting repurposing for ALI/ARDS.
Impact: This study identifies multi-target anti-inflammatory actions of cilostazol and demonstrates preclinical efficacy in ALI, suggesting a plausible therapeutic strategy for ARDS. The integrative in silico–in vivo approach provides mechanistic insight for repurposing.
Clinical Implications: Although preclinical, findings justify exploration of cilostazol as an adjunctive anti-inflammatory therapy for ALI/ARDS, with careful attention to bleeding risk and dosing. Clinical trials are needed to assess efficacy, safety, and patient selection.
Key Findings
- In silico docking predicted cilostazol binding to 10 inflammatory targets (PDK1, RAC1, PTK6, KDR/VEGFR2, EGFR, endothelin-1, caspase-3, TNF-α, NF-κB1/BTK, TLR/IRAK4) with affinities comparable to known inhibitors.
- In vivo, cilostazol reduced oxidative stress, pulmonary edema, vascular leakage, and inflammatory mediators (IL-6, TNF-α, NO, CRP, LDH, MPO, KL-6) and decreased inflammatory cell recruitment in LPS-induced ALI.
- Cilostazol downregulated mRNA expression of TNF-α, NF-κB, TLR4, and JAK/STAT3 and improved total lung capacity in rats.
Methodological Strengths
- Integrative design combining multi-target in silico docking with in vivo validation in an LPS-induced ALI rat model
- Comprehensive phenotyping including biomarkers (IL-6, TNF-α, KL-6, MPO, CRP, LDH, NO), respiratory parameters, mRNA expression, and histopathology; comparator with dexamethasone for edema
Limitations
- Preclinical single-species LPS model; human efficacy and safety unknown
- Sample size, randomization/blinding, and dose–response details not reported in the abstract; docking does not prove target engagement
Future Directions: Validate across multiple ALI/ARDS models (e.g., ventilator-induced, acid aspiration), establish dose–response and pharmacokinetics, assess bleeding risks, and progress to phase 1/2 trials to evaluate safety and preliminary efficacy.