In the heart of modern laboratories, scientists are rediscovering nature's own recipes to unlock powerful healing compounds from plants more effectively and sustainably than ever before.
For thousands of years, humans have turned to plants for medicine—from Traditional Chinese Medicine's extensive pharmacopeia to global ethnomedical systems that have provided irreplaceable therapeutic solutions. Even today, over 85% of essential botanical materia medica in traditional medical systems across 88 World Health Organization member countries originates from medicinal plants, representing a sector exceeding $100 billion in market value 1 .
Traditional medicine systems worldwide rely heavily on plant-based remedies, with documented use in over 80% of developing countries.
The global market for plant-derived medicines continues to grow, driven by increasing consumer preference for natural products.
Imagine trying to dissolve honey in water—it mixes easily. Now imagine trying to dissolve rosemary or lavender in the same water—far more difficult. This solubility challenge has long plagued scientists trying to extract beneficial compounds from plants. Traditional solvents like methanol, hexane, or chloroform work but come with significant drawbacks: they're toxic, environmentally harmful, and often destroy delicate bioactive compounds during extraction.
Natural Deep Eutectic Solvents (NaDES) represent a fundamentally different approach. These innovative liquids are created by mixing two or more natural, biodegradable components—such as sugars, amino acids, or organic acids—in specific ratios that combine to form a stable liquid with remarkable dissolving power at room temperature 6 9 .
The "eutectic" in their name comes from the Greek word "eutēktos," meaning "easily melted," referring to the dramatic lowering of melting point that occurs when these natural compounds combine 4 .
Choline chloride (melting point: 302°C) + Urea (melting point: 133°C) = NaDES (liquid at 12°C) 9
The excitement around NaDES stems from their unique combination of advantageous properties:
Composed of natural primary metabolites, they're biodegradable and have low toxicity 4 .
Their properties can be customized by adjusting components to target specific plant compounds 4 .
Researchers speculate that plants themselves might use similar natural eutectic mixtures in their cells to store and stabilize certain compounds, explaining how seeds can survive extremely dry periods and germinate after years 6 . In essence, we may be learning to use nature's own storage system to extract its valuable compounds.
Traditional extraction methods like maceration (soaking plant material in solvent) or Soxhlet extraction (continuous washing with solvent) have served science for centuries but come with significant limitations. These processes often require large volumes of organic solvents, extended processing times (hours to days), high temperatures that can damage sensitive compounds, and result in relatively low extraction efficiencies 2 .
To understand the real-world impact of NaDES, let's examine crucial research on curcumin, the celebrated bioactive compound from turmeric known for its powerful antioxidant and anti-inflammatory properties 6 .
Despite its promising health benefits, curcumin presents a major challenge: it's notoriously difficult for the human body to absorb due to its poor solubility in water. This greatly limits its therapeutic effectiveness.
Researchers created several NaDES formulations by mixing natural compounds like choline chloride with malic acid, glucose with sucrose, and other combinations in specific molar ratios, heating them at 50-80°C with stirring until clear liquids formed 6 9 .
Curcumin was added to different NaDES formulations and traditional solvents for comparison. The mixtures were agitated and allowed to reach equilibrium.
The researchers monitored curcumin stability in various NaDES formulations over time under different storage conditions.
Using simulated bodily fluids and animal models, the team investigated how effectively curcumin was absorbed when delivered via NaDES compared to conventional methods.
The compelling results demonstrated that NaDES could improve curcumin's solubility and absorption. Specifically, the formulations increased curcumin solubility up to 9-fold compared to ethanol solutions and significantly enhanced its stability 6 . When tested in animal models, certain NaDES formulations led to plasma concentrations 3-8 times higher than conventional delivery methods 6 .
| NaDES Composition | Molar Ratio | Solubility Enhancement | Key Finding |
|---|---|---|---|
| Glu:Suc | 1:1 | High | Excellent hydrophilic stability |
| ChCl:MLA | 3:1 | High | Superior to buffer or cyclodextrin solutions |
| Pro:MA:LA:WTR | 1:0.2:0.3:0.5 | Up to 9x vs. ethanol | High bioavailability in animal studies |
This experiment exemplifies how NaDES can simultaneously address multiple challenges: improving extraction efficiency, enhancing stability, and increasing the bioavailability of beneficial plant compounds—something traditional solvents cannot achieve.
Extracting bioactive compounds is only half the journey. Scientists must then identify and characterize what they've extracted. Modern analytical techniques have evolved into sophisticated systems that can handle the complex mixtures obtained from plant materials 1 5 .
Today's phytochemical analysis employs powerful hyphenated techniques that combine separation technologies with sophisticated detection methods:
Liquid chromatography separates compounds, then mass spectrometry and nuclear magnetic resonance provide structural information 5 .
An advanced setup that integrates high-performance liquid chromatography, high-resolution mass spectrometry, solid-phase extraction, and NMR for comprehensive compound identification 5 .
Combines thin-layer chromatography with biological activity assessment to pinpoint antimicrobial components 2 .
Excellent for volatile compounds, used in analysis of essential oils and fragrances.
| Technique | Key Features | Applications |
|---|---|---|
| HPLC-MS/MS | High sensitivity and selectivity | Simultaneous quantification of multiple trace compounds |
| LC-NMR | Provides detailed structural information | Identification of novel compounds |
| FTIR Spectroscopy | Rapid chemical fingerprinting | Preliminary screening of functional groups |
| GC-MS | Excellent for volatile compounds | Analysis of essential oils and fragrances |
| Reagent Category | Specific Examples | Function in Research |
|---|---|---|
| Hydrogen Bond Acceptors (HBAs) | Choline chloride, Betaine, Amino acids | Forms the base component of NADES; determines basic properties |
| Hydrogen Bond Donors (HBDs) | Sugars (glucose, fructose), Organic acids (citric, malic), Urea, Glycerol | Interacts with HBA to form eutectic mixture; tailors solvent properties |
| Plant Material | Various medicinal plants, specific plant parts (leaves, roots, bark) | Source of bioactive compounds for extraction |
| Characterization Tools | NMR spectroscopy, Mass spectrometry, Chromatography systems | Identifies and quantifies extracted compounds |
As promising as NaDES technology appears, challenges remain before it becomes standard in industry and healthcare. The high viscosity of many NaDES can complicate handling and mass transfer, though this can be mitigated by adding moderate amounts of water 4 . Additionally, while NaDES components are generally recognized as safe, comprehensive toxicological studies and regulatory approvals are needed, particularly for pharmaceutical and food applications 6 9 .
The greatest significance of this technology may lie in its ability to bridge traditional knowledge and modern science. By providing more efficient, sustainable methods to extract and preserve plant bioactive compounds, NaDES can help validate and optimize traditional remedies while making them more accessible and consistent.