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Updated: Jul 16, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
In silico drug discovery and molecular dynamics simulation for targeting neonatal pneumonia and bronchopulmonary
Xiaoqin Chen1, Qian Liu1, Bing Zhang1
1Xinxiang Central Hospital (Henan Medical University Fourth Clinical College), Neonatal Intensive Care Unit, Xinxiang, Henan, China.
Insights
This study identified Hinokiflavone and Theaflavin from Traditional Chinese Medicine as novel inhibitors of the NLRP3 inflammasome. These compounds show potential for treating neonatal pneumonia and bronchopulmonary dysplasia by reducing lung inflammation.
Area of Science:
- Computational chemistry and pharmacology
- Drug discovery and development
- Neonatal medicine
Background:
- Neonatal pneumonia and bronchopulmonary dysplasia (BPD) are leading causes of infant mortality.
- Excessive inflammation mediated by the NLRP3 inflammasome contributes to these conditions.
- Targeting the NLRP3 inflammasome offers a potential therapeutic strategy.
Purpose of the Study:
- To identify novel NLRP3 inflammasome inhibitors from Traditional Chinese Medicine (TCM) compounds.
- To evaluate the therapeutic potential of these compounds for neonatal inflammatory lung diseases.
- To utilize in silico and in vitro methods for drug discovery.
Main Methods:
- In silico drug discovery including virtual screening and molecular docking against the NLRP3 NACHT domain.
- ADMET profiling and molecular dynamics (MD) simulations to assess compound stability and properties.
- In vitro validation using cell-based assays to determine cytoprotective effects.
Main Results:
- Hinokiflavone and Theaflavin demonstrated strong binding affinity and stability with the NLRP3 NACHT domain.
- These compounds exhibited favorable ADMET profiles, suggesting good drug-likeness.
- In vitro studies confirmed the cytoprotective effects of Hinokiflavone and Theaflavin in lung epithelial cells.
Conclusions:
- Hinokiflavone and Theaflavin are promising NLRP3 inhibitors with therapeutic potential for neonatal pneumonia and BPD.
- Further preclinical studies are warranted to explore their efficacy and safety.
- TCM-derived compounds represent a valuable resource for novel anti-inflammatory drug discovery.
Background:
Neonatal pneumonia and bronchopulmonary dysplasia (BPD) are major causes of morbidity and mortality in preterm infants, driven by excessive inflammation involving the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This study employed in silico drug discovery, including virtual screening, molecular docking, ADMET profiling, molecular dynamics (MD) simulations, and MM/PBSA calculations, followed by preliminary in vitro validation to identify novel NLRP3 inhibitors from Traditional Chinese Medicine (TCM) compounds for these conditions.
Methods:
The NLRP3 NACHT domain (PDB ID: 7ALV) served as the target. A library of FDA-approved drugs and TCM-derived compounds underwent molecular docking with AutoDock Vina. Top hits were evaluated for ADMET properties using SwissADME, pkCSM, and admetSAR. Selected complexes (Hinokiflavone, Theaflavin, Sciadopitysin, Liquiritin apioside, Tigogenin) were subjected to 200 ns all-atom MD simulations in GROMACS and MM/PBSA binding free energy analysis. In vitro cytoprotective effects were assessed via MTT assay in LPS-stimulated BEAS-2B and MLE-12 lung epithelial cells, with glyburide as positive control.
Results:
Hinokiflavone and Theaflavin exhibited the strongest docking scores (-10.8 and -10.4 kcal/mol), superior MD stability (lowest RMSD: 0.21 ± 0.02 nm and 0.23 ± 0.03 nm; high hydrogen bond occupancy: 78% and 82%), and most favorable MM/PBSA binding energies (-55.8 and -55.2 kcal/mol), driven by van der Waals and electrostatic interactions. They showed acceptable ADMET profiles with high intestinal absorption and low BBB penetration. In vitro, Hinokiflavone restored cell viability to 89.6% ± 3.2% at 50 µM (comparable to glyburide at 91.2% ± 2.8%), while Theaflavin reached 82.4% ± 3.9%, demonstrating dose-dependent protection against LPS-induced cytotoxicity.
Conclusion:
Hinokiflavone and Theaflavin emerge as promising NLRP3 inhibitors with stable binding to the NACHT domain and cytoprotective effects in lung epithelial cells. These TCM-derived compounds warrant further preclinical investigation as potential targeted therapies to mitigate inflammation in neonatal pneumonia and BPD.
