| Summary: | A green extraction method was developed using deep eutectic solvent extraction for the polysaccharide from <i>Acanthopanax senticosus</i> (<i>A. senticosus</i>). Among the eight types of DES prepared, the DES with a ratio of 1:4 L-malic acid to L-proline was found to be a suitable extraction solvent based on the extraction efficiency. The extraction parameters were optimized by Plackett–Burman and response surface methodology (RSM). The best extraction conditions were found for L-malic acid. Under the conditions of an L-malic acid/L-proline ratio of 1:4, ultrasonic power of 240 W, material–liquid ratio of 31.068 g/mL, water content of 32.364%, extraction time of 129.119 min, and extraction temperature of 60 °C, the extraction rate of <i>A. senticosus</i> polysaccharides was 35.452 ± 0.388 mg-g<sup>−1</sup>. This rate was higher than that of polysaccharides obtained by hot water extraction (13.652 ± 0.09 mg-g<sup>−1</sup>). The experimental results were best fitted by the quasi-secondary kinetic model when compared to two other kinetic models. Electron microscopic observations showed that DESs were more destructive to plant cells. The polysaccharide extracted from DESs had more monosaccharide components, a lower molecular weight, a higher antioxidant capacity, and superior anti-glycation activity compared to polysaccharides extracted from water (ASPS-PW). This study demonstrates the effectiveness of DESs in obtaining polysaccharides from <i>A. senticosus</i>.
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