The present study optimized the ultrasound assisted extraction (UAE) conditions using Box-Behnken design (BBD) with response surface methodology (RSM) and evaluated the antioxidant activity of total flavonoids from Cryptotaenia japonica Hassk. The results showed that the optimum conditions were 55% ethanol concentration, 1:30 g/mL solid to solvent ratio, 400 W ultrasound power, 70 min extraction time and 3 cycles. Under these optimum conditions, the extraction yield of total flavonoids was 33.110 ± 0.742 mg/g DW (dry weight), which was well consisted with value predicted by the model. The RSM optimized extract was subsequently checked for antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, hydroxyl scavenging assay and reducing power assay. Under the flavonoid concentration of 3.0 mg/mL, antioxidant scavenging activity were of 79.87±2.7% and 71.60±2.6% for DPPH and hydroxyl assay while for reducing power and absorbance of 1.200±0.053 was obtained. Furthermore, the composition in antioxidants were investigated, and the luteolin and apigenin were determined. The results indicated that ultrasound assisted extraction is a promising technique for extraction of flavonoids from C. japonica Hassk and the flavonoids could be explored as a potential antioxidant agent for use in medicine or functional foods.

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