Tailored biphasic deep eutectic solvents for one-step high-efficient extraction and separation of Hedyotis diffusa bioactive ingredients

The simultaneous extraction of bioactive compounds with differing polarities from plant matrices remains a significant challenge. This study was conducted to overcome the drawbacks of traditional extraction methods for the precious medicinal herb Hedyotis diffusa (HD), such as their low extraction efficiency, incapacity to completely utilize HD, and instability of active ingredients. To this end, a biphasic DES with ultrasound assistance was developed for the simultaneous extraction of high-value iridoids and triterpenes from HD. Following a thorough screening process that encompassed 56 two-phase combinations, the choline chloride-acetic acid (ChCl-Aa)/L-menthol-n-octanoic acid (Men-Oa) system was identified as the optimal formulation. Through the implementation of polarity regulation and response surface methodology, this optimal biphasic DES attained extraction yields of 15.65 ± 0.19 mg/g for five target compounds under mild conditions (41.65 °C, 30.71 min, liquid-solid ratio 15.73 mL/g, hydrophilic-to-hydrophobic phase volume ratio 0.77), which is a 2–3-fold improvement over traditional extraction methods. Characterization results indicated that the DES facilitated target release primarily by forming hydrogen-bond networks, which not only enhanced solubilization but also contributed to the disruption of cell wall. This disruptive effect was further augmented by the biphasic interface generated under ultrasonication, leading to significantly improved extraction efficiency. This strategy establishes a green and efficient approach for the valorization of plant resources.