Pro-regenerative potential of Artemisia annua L. essential oil: Toward a plant-derived ingredient for wound healing applications

Artemisia annua L. is extensively cultivated for artemisinin, generating large amounts of aerial biomass, while its essential oil (AAO) remains underutilized. This study aims to evaluate the regenerative potential of AAO and to elucidate its mechanism, so that to support by-product valorization for wound healing and tissue repair applications. AAO was extracted from aerial parts and characterized by GC–MS, which identified 31 major constituents dominated by mono- and sesquiterpenes, with artemisia ketone as a representative abundant component. Regenerative efficacy was assessed in a zebrafish caudal fin amputation model and mechanistic insights were obtained by integrating network pharmacology with transcriptomics and experimental validation. AAO significantly accelerated fin regrowth and tissue restoration, whereas the glucocorticoid control (beclomethasone) impaired regeneration. Network pharmacology identified four core targets (HSD11B1, PA2G4, TJP1, SLC6A3) linked to inflammation–autophagy–regeneration processes. Transcriptomic profiling and in vivo validation showed that AAO timely attenuated early inflammatory responses, evidenced by reduced neutrophil accumulation and downregulation of pro-inflammatory genes, and dynamically regulated autophagy, characterized by early enhancement followed by restoration of homeostasis. Subsequently, AAO robustly activated pro-regenerative gene programs and promoted fin restoration. Overall, AAO exhibits dual anti-inflammatory and pro-regenerative activities mediated by spatiotemporal coordination of the inflammation–autophagy–regeneration cascade, supporting its development as a plant-derived functional ingredient and providing a feasible route to increase the economic value of Artemisia annua L. biomass streams. • AAO transforms an agricultural by-product into a value-added wound healing agent. • It accelerates tissue repair without the suppression effects of conventional drugs. • Chemical profiling and multi-method validation support its standardized development.