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Background: In this study, ultrasonic-microwave-assisted extraction (UMAE) was first applied to extract polysaccharides from the leaves of mulberry (PLM). The optimal conditions for polysaccharides extraction were determined by response surface methodology (RSM) along with central composite design (CCD) based on the singlefactor experiments. Extraction temperature (°C), extraction time (s), pH value, and ratio of water to raw material were investigated. Also, the antioxidant activities of PLM with UMAE were evaluated. Results: According to statistical analysis, extraction temperature and pH value significantly affected extraction yield. The central composite design (CCD) showed that polynomial regression models were in good agreement with the experimental results with the coefficients of determination of 0.9263 for PLM. The optimal conditions were extraction temperature 76°C, extraction time 807 s, pH value 6.16 and the ratio of water to raw material 40:1, and the maximal yield of PLM was 10.29 ± 0.41(%). Meanwhile, DPPH radical-scavenging at EC50 values of PLM was found to be 128.3 μg/ml. Conclusion: Under the optimal conditions, the experimental values agreed with value predicted by the model. The results suggested that UMAE could be used for the extraction of PLM, and the polysaccharides from mulberry leaves have significant antioxidant activities, which can be used as a source of potential antioxidant.
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