Green and Efficient Extraction of Polyphenols From Lonicera caerulea L. Berries and Evaluation of Their Antioxidant and Lipid‐Lowering Activities

The demand for sustainable methods to extract bioactive compounds from fruits is increasing, yet conventional extraction methods are limited by their reliance on large amounts of organic solvents, limiting their widespread application. Therefore, we evaluated a deep eutectic solvent (DES)-ultrasound-assisted extraction to efficiently extract phenolic compounds from Lonicera caerulea L. berries. Using single-factor experiments and response surface methodology, the optimal conditions were determined: A DES composed of choline chloride and 1,3-butanediol at a 1:5 molar ratio, with 29% water content, a solid-liquid ratio of 1:41 g/mL, and ultrasonication for 50 min. This method yielded 68.63 ± 0.46 mg gallic acid/g of total polyphenols, a 1.5-fold increase over the conventional solvent (50% ethanol). Furthermore, UHPLC-Q-TOF-MS/MS analysis confirmed the presence of 31 phytochemicals in the extract, including cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside, chlorogenic acid, procyanidin B2, rutin, and quercitrin, among others. Scanning electron microscopy analysis confirmed the synergistic mechanism of DES permeation and ultrasound-induced cell wall disruption, and the mechanism of DES formation was studied by Fourier transform infrared spectroscopy. Further studies revealed that the extract exhibited significant antioxidant activity, with IC₅₀ values of 8.57 ± 0.19 µg/mL, 409.13 ± 6.77 µg/mL, and 123.17 ± 3.25 µg/mL for DPPH•, •OH, and ABTS⁺• assays, respectively, and demonstrated pancreatic lipase inhibition with an IC₅₀ of 4.31 ± 0.12 mg/mL. In the zebrafish model of non-alcoholic fatty liver disease, the extract (200 µg/mL) significantly reduced hepatic lipid accumulation, and decreased total cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase levels by 64%, 60%, 60%, and 55%, respectively, confirming potent lipid-lowering and hepatoprotective efficacy. Overall, DES combined with ultrasound-assisted extraction could serve as an eco-friendly method for recovering high-value compounds from fruits and their byproducts.