Unravelling the therapeutic potential of chrysin against ischemic stroke and post-stroke cognitive impairment: a network pharmacology and in-silico perspective.

Ischemic stroke (IS) is a cerebrovascular disorder that, if left untreated, can lead to secondary neurodegeneration and Post Stroke Cognitive Impairment (PSCI). Current therapies offer a narrow time window, highlighting the need for alternative approaches. Flavonoids, known for their neuroprotective properties, are promising candidates. Chrysin, a flavone with multiple pharmacological activities, was investigated for its therapeutic role in IS and PSCI. Pharmacokinetic and toxicological profiles were assessed using Schrodinger and ProTox III. Target screening was performed via Swiss Target Prediction-STITCH for chrysin and Gene Cards-OMIM for disease targets. Protein-Protein Interaction (PPI), Gene Ontology (GO), and KEGG pathway analyses were conducted using STRING and DAVID. Network construction was done in Cytoscape 3.10.3. Density Functional Theory (DFT) calculations used Schrodinger Jaguar to assess molecular reactivity. Molecular docking and Molecular dynamics simulation studies were also performed using Schrodinger. Chrysin was associated with 134 targets, while IS and PSCI had 3024 and 7472 targets, respectively, with 109 overlapping targets. GO and KEGG analyses showed chrysin’s influence on key cell growth and apoptosis pathways. DFT analysis indicated a HOMO-LUMO energy gap of 0.164342 Hartree, suggesting high reactivity and potential for electron transfer. Docking studies revealed strong binding affinity of chrysin to SIRT1 (-5.108 kcal/mol) and PGC1α (-9.072 kcal/mol). Molecular dynamics confirmed chrysin’s stable interaction, particularly with SIRT1. Chrysin demonstrates potential as a therapeutic agent for IS and PSCI by modulating cellular longevity, oxidative stress, and apoptosis pathways, including MAPK and FoxO signaling.