Natural deep eutectic solvents combined with COSMO-RS model for efficient extraction of essential oil from Fructus Aurantii: Theoretical screening, process optimization, biological activity and mechanism

Traditional extraction methods of essential oil suffer from limitations such as low extraction efficiency or the use of toxic solvents, which fail to meet the principles of green chemistry. To address these issues, this study established a high-efficiency, eco-friendly method for extracting essential oils from Fructus Aurantii by integrating natural deep eutectic solvents (NADES) with the COSMO-RS tool. We initially screened 18 types of NADESs through theoretical analysis (COSMO-RS) and experimental validation, ultimately identifying the optimal extraction solvent (Gly-Laa, molar ratio 1:3). Subsequently, the extraction process was optimized using a Box-Behnken design (BBD) approach. The results revealed that the optimal conditions were 10 % water content, a 5:1 (g/g) liquid/solid ratio, and 7 h extraction time, respectively—achieved a maximum yield of 2.82 %. This represents a 4.7-fold increase compared to steam distillation (0.6 %) and a 1.76-fold enhancement over petroleum ether extraction (1.6 %). Furthermore, the extraction mechanism was investigated through MD simulations and RDG analysis. The results indicated that NADES enhanced its interactions with limonene via hydrogen bonding (average bond length: 0.14–0.22 nm) and van der Waals forces. Finally, the biological activities of the extracted essential oil were analyzed and compared. The results revealed that the NADES-extracted essential oil exhibited superior antioxidant capacity (DPPH and ABTS scavenging rates >80 %), significant antibacterial efficacy against pathogens such as Staphylococcus aureus (inhibition zone diameter >10 mm), and demonstrated notable anti-tumor activity. In summary, the combination of NADES and COSMO-RS model is a sustainable and efficient essential oil extraction strategy.