Phytosterols from Rosaceae Species as Dual Modulators of Neuroinflammation and Induced Pluripotency

Abstract

Neuroinflammation is a central pathological hallmark of numerous neurodegenerative disorders, often linked to oxidative stress, immune dysregulation, and neuronal dysfunction. Recent advances in regenerative medicine highlight induced pluripotent stem cells (iPSCs) as a powerful tool for cellular reprogramming and neurorestoration. In this study, we explored the therapeutic potential of phytosterols derived from Rosaceae species as dual modulators of neuroinflammation and pluripotency induction. Transcriptomic datasets comprising 42 patient samples (GSE176101, GSE200674, and GSE225031) were analyzed to identify differentially expressed genes (DEGs) associated with neuroinflammatory signaling and stemness regulation. Functional enrichment and pathway analyses revealed significant involvement of inflammatory cascades, oxidative stress responses, and neuroprotective mechanisms. Network pharmacology and protein-ligand interaction studies identified EGFR, ACHE, and PRKCG as critical molecular targets. Molecular docking and molecular dynamics simulations further validated the stable binding affinity of Rosaceae-derived phytosterols with these proteins. Collectively, our findings suggest that phytosterols from Rosaceae species hold promise as multifunctional agents capable of attenuating neuroinflammation while simultaneously promoting iPSC generation, thus providing a novel framework for therapeutic strategies in neurodegenerative disease management.

Keywords: Induced pluripotent stem cells (iPSCs); Molecular docking simulation; Neuroinflammation; Neuronal dysfunction; Phytosterols.