Selective recovery of Ginkgo biloba flavonoids and simultaneous removal of ginkgolic acids via deep eutectic solvent‑based liquid‑liquid extraction

Abstract This study develops a green and efficient two-phase deep eutectic solvents (DESs) liquid–liquid extraction (LLE) method, utilizing hydrophilic DESs for Ginkgo biloba flavonoids (GBFs) extraction and hydrophobic DESs for G. biloba acid (GAs) removal from Ginkgo leaf. Initially, COSMOtherm software was employed to screen 80 DESs through activity coefficient calculations, identifying suitable hydrophilic and hydrophobic DESs. Among the COSMOtherm-screened and experimentally validated DESs, the hydrophilic DESs composed of Methyl- β -cyclodextrin and 1,4-butylene Glycol (M- β -CD/BDO) with a mass ratio of 1:5 was selected, demonstrated higher extraction efficiency for GBF. Under the optimal conditions, the maximum extraction yield of GBFs reached 10.06 ± 0.14 mg/g. Subsequently, oleic acid/lauryl alcohol (5:1) was applied to remove five types of GAs from the M‑ β ‑CD/BDO extract using LLE. Through the optimization of LLE conditions, the removal rate of GAs reached 86.28 ± 1.21%, while the loss rate of GBFs was only 6.46 ± 0.23%. Finally, hybrid density functional theory (DFT) calculations, including the measurement of the binding energy (E int ), and scanning electron microscopy (SEM) were employed to elucidate the mechanism by which M‑ β ‑CD/BDO enhances the extraction efficiency of GBFs. Additionally, molecular dynamics simulations were conducted to quantitatively analyze the diffusion coefficients of 13 Ginkgo compounds in M‑ β ‑CD/BDO and OleA/Lau systems.