Aqueous bio-based hydrotropic solutions for green extraction of glycyrrhizic acid from licorice: experimental investigation and mechanistic insights

Abstract

Aqueous bio-based hydrotropic solutions (ABHS) were investigated as green solvents for extracting glycyrrhizic acid (GA), a major amphiphilic triterpenoid saponin from licorice. Conventional and bio-based hydrotropes were screened under ultrasound-assisted extraction, with pentane-1,2-diol (PED) identified as the most effective solvent. Under optimized conditions (67.9% ABHS concentration, liquid–solid ratio of 49.9 mL g⁻¹, extraction time of 17.0 min, and extraction temperature of 70 °C), ABHS achieved high GA extraction yield of 79.43 mg g⁻¹, markedly outperforming conventional aqueous alcohols (≈49 mg g⁻¹) and reported eutectic solvents (45.47–61.29 mg g⁻¹). Extraction kinetics followed a second-order model, with a low apparent activation energy of 19.84 kJ mol⁻¹, indicating a diffusion-controlled extraction process. Quantum chemical analyses, including electrostatic potential mapping, interaction region indicator analysis, and binding energy evaluation, revealed cooperative stabilization of both polar glycosidic units and weakly polar triterpenoid domains of GA in ABHS, with a calculated binding energy of −19.798 kcal mol⁻¹, significantly stronger than those observed for water (−12.137 kcal mol⁻¹) and ethanol (−15.307 kcal mol⁻¹). An integrated macroporous resin-based strategy enabled efficient GA recovery with a recovery efficiency of 92.98% and high GA content (80.31%), while maintaining stable extraction performance and solvent recovery above 95.50% over three reuse cycles. Furthermore, GA-enriched fraction obtained using ABHS exhibited enhanced nitric oxide inhibitory activity without detectable cytotoxic effects on normal human cells, as supported by molecular docking analysis. In this context, the present study establishes ABHS as efficient, sustainable, and mechanistically transparent platforms for GA extraction, offering a promising green strategy for amphiphilic triterpenoid saponins.