Integrated Experimental and Computational Insights into the Anti-Inflammatory Potential of Flower-Derived Exosome-Like Nanoparticles Targeting the NF-κB Pathway

Sreyoshi RouthVenkatraman Manickam^*

• VIT University, Vellore, India

Dysregulated inflammation underlies numerous chronic pathologies, with the NF-κB p65–p50 heterodimer acting as a pivotal transcriptional regulator mediating different inflammatory responses. Consequently, inhibiting NF-κB nuclear translocation has emerged as a promising strategy in anti-inflammatory drug development. While floral extracts have been widely used, recent advancements highlight the therapeutic potential of flower derived exosome like nanoparticles as promising cell free therapeutics owing to their enhanced biocompatibility, and stability. Here, we report the isolation and characterization of exosome-like nanoparticles (ELNs) from three ethnomedicinal flowers, followed by comprehensive GC–MS-based metabolomic profiling. The ELNs exhibited robust radical scavenging capacity, indicative of potent antioxidant activity followed by cell viability assay, ELISA, and gene expression studies to elucidate the anti-inflammatory efficacy of isolated exosomes. To further delineate the underlying molecular mechanisms of ELN encapsulated metabolites interacting with NF-κB pathway, key metabolites were computationally screened against crystallized p65–p50 heterodimer, and the most promising ligands were subjected to molecular dynamics simulations to investigate binding stability and interaction dynamics. Both docking scores and simulation trajectories strongly supported stable, high-affinity interactions consistent with NF-κB pathway inhibition. Overall, the combined experimental and computational findings in the study represent the first comprehensive data of floral ELN bioactives offering significant translational potential of floral nanovesicles as a new class of biocompatible, cell-free nanotherapeutics for anti-inflammatory drug discovery.