Title:Screening of Phytocompounds Against the NF-kB Pathway Genes and Lung Elevated Proteins Associated with Acute Respiratory Distress Syndrome
Volume: 20
Issue: 2
Author(s): Muruganantham Bharathi, Bhagavathi Sundaram Sivamaruthi, Athit Bunyakitcharoen, Periyanaina Kesika*Chaiyavat Chaiyasut*
Affiliation:
- Office of Research Administration, Chiang Mai University, Chiang Mai, 50200,
Thailand
- Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy, Chiang Mai University,
Chiang Mai, 50200, Thailand
Keywords:
Reactive oxygen species, acute respiratory distress syndrome, PPI network, biomarker genes, NF-kB, genkdaphine, edulisin III.
Abstract:
Introduction: Acute Respiratory Distress Syndrome (ARDS) is the pathophysiologic
state of the inflammatory response to lung injury characterized by alveolar epithelial cell damage
and increased cytokine production and accumulation in the lungs.
Objectives: The current study was performed to identify the molecular mechanisms of ARDS
related to the proteins elevated in the lung (PEL) and NF-κB pathway regulatory genes (GRNF).
In addition, the phytocompounds were screened to inhibit the representative target genes and
proteins associated with ARDS.
Materials and Methods: We implemented STRING v11.5 and Network Analyst 3.0 to construct
the protein-protein interactions (PPI) network. CytoScape v3.8.2 and DisGeNet v7.3.0 were
utilized to visualize and identify genes involved in respiratory diseases. The Cytohubba module
was utilized to identify the hub genes from the constructed PPI network. Autodock Vina and
Discovery Studio Visualizer v19.1.0.1828 were utilized for the molecular docking analysis.
Results: The PPI network was constructed with the GRNF genes. Fifty-four genes are identified
as biomarkers involved in respiratory diseases (BMRD). About 191 PEL were identified from
the human protein atlas database and constructed the PPI network. The interactions between the
PPI network of BMRD and PEL were analyzed. The top 100 hub genes and the signaling genes
were identified. Based on the identified signaling genes through the PPI network of BMRD and
PEL, the metabolic pathway was elucidated, which causes ARDS via NF-κB activation. The
ARDS targets (ACVRL1, IKKβ, ITGAL, ITGB2, TGFβR1, and TGFβR2) were selected for the
molecular docking study. One hundred and thirty-five chemical compounds from Allium sativum,
Alstonia scholaris, Ammi visnaga, Artemisia vulgaris Linn., Houttuynia cordata, and
Ocimum gratissimum Linn. were retrieved and used for docking against selected ARDS targets.
Among them, genkdaphine from A. sativum inhibited ACVRL1 (binding affinity of -9.2
kcal/mol, and RMSD of 2.607Å), ITGAL (binding affinity of -9.1 kcal/mol, and RMSD of
1.69Å), ITGB2 (binding affinity of -7.9 kcal/mol, and RMSD of 2.184Å), TGFβRI (binding
affinity of -8.5 kcal/mol, and RMSD of 1.807Å), and TGFβRII (binding affinity of -8.2
kcal/mol, and RMSD of 1.647Å). Edulisin III from A. visnaga inhibited the IKKβ (binding affinity
of -7.4 kcal/mol, and RMSD of 2.223Å).
Conclusion: Genkdaphine and edulisin III may be the therapeutics for treating ARDS. However,
further studies are needed to warrant the benefits of genkdaphine and edulisin III in treating
ARDS. The study's findings may aid in developing new therapeutic approaches to improve the
health status of ARDS-affected patients.
