| Summary: | The <i>Artemisia argyi</i> leaf (AL) has been used as a traditional medicine and food supplement in China and other Asian countries for hundreds of years. Phytochemical studies disclosed that AL contains various bioactive constituents. Among bioactive constituents, phenolic acids have been recognized as the main active compounds in AL. To the best of our knowledge, no research has been focused on extraction method for the bioactive phenolic acids from AL. Nowadays, deep eutectic solvents (DESs) are emerging as a new type of green and sustainable solvent for efficient extraction of bioactive compounds from natural products. In the present study, an environmentally friendly extraction method based on DESs was established to extract bioactive phenolic acids from ALs. Diverse tailor-made solvents, including binary and ternary DESs, were explored for simultaneous extraction of four phenolic acids (3-caffeoylquinic acid, 3,4-di-<i>O</i>-caffeoylquinic acid, 3,5-di-<i>O</i>-caffeoylquinic acid, and 4,5-di-<i>O</i>-caffeoylquinic acid) from AL. The results indicated that the ternary DES composed of a 2:1:2 molar ratio of choline chloride, malic acid, and urea showed enhanced extraction yields for phenolic acids compared with conventional organic solvents and other DESs. Subsequently, the extraction parameters for the four phenolic acids by selected tailor-made DESs, including liquid−solid ratios, water content (%) in the DESs, and extraction time, were optimized using response surface methodology and the optimal extraction conditions were: extraction time, 23.5 min; liquid−solid ratio, 57.5 mL/g (mL of DES/g dry weight of plant material); water content, 54%. The research indicated that DESs were efficient and sustainable green extraction solvents for extraction of bioactive phenolic acids from natural products. Compared to the conventional organic solvents, the DESs have a great potential as possible alternatives to those organic solvents in health-related areas such as food and pharmaceuticals.
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