Identification of PPIA, DPP4, and ITK as Potential Targets of Pterostilbene in Abdominal Aortic Aneurysm: A Network Pharmacology and Molecular Docking Study.

BACKGROUNDPterostilbene is a polyphenolic compound with antioxidant and anti-inflammatory properties. This study aims to explore its potential therapeutic effects on Abdominal Aortic Aneurysm (AAA).

METHODSThe Gene Expression Omnibus (GEO) database was accessed to obtain single- cell sequencing data and transcriptome datasets to identify Differentially Expressed Genes (DEGs) in AAA. The DEGs were further intersected with predicted targets of pterostilbene to identify common genes, which were considered core genes for functional enrichment analysis and Gene Set Enrichment Analysis (GSEA). Molecular docking and 100 ns Molecular Dynamics (MD) simulations were then performed to evaluate binding affinity and stability.

RESULTSPPIA, DPP4, and ITK were identified as overlapping genes associated with both pterostilbene and AAA. A single-cell atlas revealed their specific expression patterns across different cell types. The three genes were also correlated with IL6/JAK/STAT3, inflammatory response, and immune-related pathways. Molecular docking showed binding affinities ranging from -5.66 to -7.11 kcal/mol, and 100 ns MD simulations revealed stable binding conformations for all three targets.

DISCUSSIONThe present multi-omics analysis suggests that pterostilbene may exert therapeutic effects on AAA by modulating inflammation- and immune-related pathways, providing a hypothesis-generating basis for further investigation.

CONCLUSIONThis hypothesis-generating study proposes that pterostilbene may exert therapeutic effects on AAA by targeting PPIA, DPP4, and ITK and modulating inflammation- and immune-related pathways. However, these computational findings require further experimental validation.