Ultrasound‐Assisted Combined With Natural Ternary Deep Eutectic Solvent Extraction Method for the Green Extraction of Squalene From Strobilanthes tonkinensis

ABSTRACT Plant‐derived squalene represents a vital natural source of high additional value product, yet conventional extraction methods are often hindered by their reliance on large volumes of organic solvents, limiting their widespread application. Here, we developed a pioneering green extraction platform integrating ultrasonic‐assisted extraction with ternary deep eutectic solvents (UAE–TDESs), specifically engineered for efficient squalene recovery from plant biomass. Through systematic optimization via response surface methodology (RSM), we achieved a maximum squalene yield of 331.79 µg/g dry weight (DW) under optimal conditions: TDESs (betaine: vitamin C: glycerol, 2:1:1 molar ratio), 69°C extraction temperature, 41 min duration, 31 mL/g liquid–solid ratio, and 39% TDES water content. Comparative analysis demonstrated a 2.9% yield enhancement over the n ‐hexane extraction (322.58 µg/g DW) while eliminating all toxic organic solvents. Mechanistic investigations using scanning electron microscopy (SEM) and x‐ray diffraction (XRD) revealed that TDESs induce lignin dissolution while ultrasonication disrupted cellular architecture through cavitation‐driven mechanical shear. Collectively, this work established a robust, sustainable framework for TDESs mediated recovery of bioactive compounds, demonstrating significant potential for broader industrial application.