Experimental Characterization Combined with Computational Network Analysis of Metabolites Associated with Chrysanthemum morifolium-derived exosome-like Nanoparticles in Predicting Potential AKI-relevant Targets.

Exosome like nanoparticles (ELNs) derived from plants and plant products have emerged as promising nanotherapeutics owing to their enhanced biocompatibility, stability, and minimal toxicity. Despite the widespread use of Chrysanthemum morifolium in traditional Chinese medicine, the pharmacological significance and mechanistic role of ELNs derived from this flower (CELNs) remains largely unexplored in the context of acute kidney injury (AKI). In the present study, CELNs were isolated, characterized and their encapsulated bioactive metabolites were identified using GC-MS analysis. To explore the potential mechanisms underlying CELN-mediated therapeutic intervention against AKI, we employed an integrative computational approach combining network pharmacology and molecular dynamic simulation. Putative AKI-related targets associated with the CELN metabolites were retrieved from public databases (SEA and STP), and the 49 final overlapping targets were selected. A network pharmacology study involving gene, pathway enrichment studies and protein-protein interactions were performed. Subsequently, computational docking and MD simulations suggested that selected CELN metabolites (2-Methyl-5 H-dibenz[b, f]azepine and n-Hexadecanoic acid) may bind to hub targets (ALOX5, ALOX15, JAK2, TNF-ɑ, and EPHX2) involved in pathways linked to AKI progression; these predictions require experimental confirmation. Overall, this study integrates experimental metabolite identification with computational analyses to provide preliminary mechanistic insights into the potential role of CELNs in modulating pathways associated with AKI and improve renal recovery trajectories.