Deep eutectic solvents, or DESs, are mixtures of two or more substances that, when combined in particular ratios, form a liquid with a melting point far lower than any of the individual components. They are often described as close cousins of ionic liquids, but with a crucial advantage: their ingredients can be cheap, abundant, biodegradable, and even food-grade. Because their polarity, hydrogen-bonding ability, and hydrophobicity can be tuned simply by swapping the constituent molecules, DESs have become attractive candidates for selectively dissolving specific natural products. The research team, led by Huixin You and Dongting Huang of Fujian University of Traditional Chinese Medicine together with colleagues including Wei Xu of Fujian Health College, exploited this tunability in a two-phase liquid–liquid extraction scheme designed specifically for ginkgo chemistry.

The first challenge the team faced was choosing the right solvent pair from an enormous design space. Rather than laboriously testing candidates one by one at the bench, the researchers turned to COSMOtherm, a computational tool that predicts how molecules interact with liquids by calculating activity coefficients from fundamental quantum chemistry. Screening eighty candidate deep eutectic solvents in silico, they identified promising hydrophilic systems for flavonoid extraction and hydrophobic ones for ginkgolic acid removal. This computational pre-selection dramatically narrowed the field before a single experiment was run, a strategy that saves time, reduces chemical waste, and illustrates how modern solvent design increasingly begins on the computer rather than in the fume hood.

Among the candidates validated experimentally, a hydrophilic DES composed of methyl-β-cyclodextrin and 1,4-butylene glycol in a mass ratio of 1:5 emerged as the standout performer for recovering ginkgo flavonoids. Methyl-β-cyclodextrin is a ring-shaped sugar molecule whose hollow, hydrophobic interior cavity can encapsulate flat, aromatic guests such as flavonoids, while its outer surface remains water-friendly. Pairing this molecular host with butylene glycol creates a solvent that can coax flavonoids out of plant tissue and hold them in solution. Under optimised conditions, the team achieved a maximum extraction yield of 10.06 milligrams of flavonoids per gram of material, a figure that demonstrates the practical viability of this cyclodextrin-based solvent for real plant extracts.

With the flavonoids recovered, the researchers then confronted the second half of the problem: ginkgolic acids. These long-chain phenolic acids are structurally related to compounds found in poison ivy and are responsible for allergic reactions in sensitive individuals, which is why pharmacopoeial standards limit their content in ginkgo products. To remove them, the team applied a hydrophobic deep eutectic solvent made from oleic acid and lauryl alcohol in a 5:1 ratio. Because this solvent forms its own phase and does not mix with the hydrophilic extraction medium, the two liquids could be brought into contact, allowing the ginkgolic acids to partition preferentially into the oily hydrophobic phase while the valuable flavonoids stayed behind.

The selectivity achieved in this second step is the study’s headline result. After optimising the liquid–liquid extraction conditions, the oleic acid–lauryl alcohol system removed 86.28 percent of five types of ginkgolic acids from the flavonoid-rich extract, while sacrificing only 6.46 percent of the flavonoids. That imbalance—large-scale removal of the undesirable compounds with minimal collateral loss of the desirable ones—is precisely what industrial downstream processing demands. It suggests that a carefully matched pair of deep eutectic solvents could in principle replace multi-step chromatographic or organic-solvent-based purification in the production of safer ginkgo ingredients.

Curious about why the cyclodextrin solvent worked so well, the researchers probed the underlying mechanism with two complementary techniques. First, they ran hybrid density functional theory calculations, a quantum-chemical method that allowed them to measure the interaction energy between the solvent components and the flavonoid molecules, revealing the strength and nature of the binding that anchors flavonoids in the DES. Second, scanning electron microscopy provided visual evidence of how plant material interacts with the solvent system at the microscopic scale. Together, these approaches support the idea that inclusion complexation between methyl-β-cyclodextrin’s cavity and the flavonoid scaffold underpins the enhanced extraction efficiency, turning an empirical observation into a mechanistically grounded explanation.

The team went further, deploying molecular dynamics simulations to track how thirteen different ginkgo compounds move through both the hydrophilic and hydrophobic solvent systems. By quantifying diffusion coefficients in the M-β-CD/BDO and oleic acid–lauryl alcohol media, the simulations offered a dynamic picture of transport behaviour, complementing the static energetic analysis from the DFT calculations. This combination of computational thermodynamics, quantum chemistry, microscopy, and molecular simulation represents a thorough multiscale interrogation of a separation process, and it points toward a future where extraction chemistries can be predicted and optimised computationally before scaling up.

The implications extend well beyond ginkgo. Herbal medicine, functional foods, and nutraceutical industries constantly wrestle with the dilemma of extracting trace beneficial compounds from complex plant matrices while excluding unwanted or toxic co-extractants. Conventional processes often consume large volumes of petrochemical solvents, generate problematic waste, and demand energy-intensive evaporation steps. Deep eutectic solvents built from substances as benign as cyclodextrins, glycols, fatty acids, and alcohols promise greener alternatives, and their ability to be tailored for specific tasks—as this study’s paired hydrophilic and hydrophobic systems demonstrate—makes them versatile tools for selective molecular separation across the natural products landscape.

The work, supported by the National Natural Science Foundation of China and the Fujian Provincial Department of Science and Technology, remains at the laboratory stage, and translating a bench-scale process into industrial manufacturing will require further work on solvent recovery, cost, and regulatory acceptance. Even so, the study offers a compelling template: screen computationally, validate selectively, explain mechanistically. If that recipe holds for other medicinal plants and other problematic contaminants, the era of sustainable, precision extraction may arrive not with dramatic new machinery, but with elegantly designed liquids that know exactly which molecules to keep and which to discard.

Subject of Research: Deep eutectic solvent-based liquid-liquid extraction for selective recovery of Ginkgo biloba flavonoids and removal of ginkgolic acids

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

Article References: You, H., Huang, D., Han, H., Shen, H., Liu, Y., Li, H., & Xu, W. (2026). Selective recovery of Ginkgo biloba flavonoids and simultaneous removal of ginkgolic acids via deep eutectic solvent‑based liquid‑liquid extraction. npj Science of Food. https://doi.org/10.1038/s41538-026-01176-w

Image Credits: AI Generated

DOI: 10.1038/s41538-026-01176-w

Keywords: deep eutectic solvents, Ginkgo biloba, flavonoids, ginkgolic acids, liquid-liquid extraction, COSMOtherm, cyclodextrin, green chemistry, density functional theory, molecular dynamics, food science, herbal medicine