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Optimum conditions for ultrasonic‐assisted extraction (UAE) of total phenolic (and total flavonoid compounds (TPC & TFC) and antioxidant activity from aerial parts of Saccocalyx satureioides have been investigated using response surface methodology (RSM). The Box–Behnken design was used to investigate the effects of three independent variables: Temperature, time, and solvent/matter “mL/g d.w.” ratio. In this study, total phenolics and total flavonoids extracts were investigated for their antioxidant activity using two different and complementary assays: the DPPH• (2,2‐diphenyl‐1‐picrylhydrazyl) free radical scavenging and the ferric reducing antioxidant power (FRAP). Optimized conditions of UAE were determined for TPC, TFC, and antioxidant capacity (DPPH, FRAP) at once. The results suggested that extraction with absolute methanol to dry matter ratio of 70/1 mL/g for 40.0 min at 43.21°C were the optimal conditions for this combination of variables. Hence, the optimal solution results for the investigated variables were as follows: TPC = 2.416 g/100 g, TFC = 0.440 g/100 g, DPPH (IC50 = 0.022 mg/mL), FRAP (IC50 = 0.760 mg/mL). The experimental values agreed with those predicted ones within a 95% confidence level, thus indicating the suitability of RSM in optimizing the UAE of phenolic compounds from S. satureioides. The results indicated also that optimization of extraction conditions in this plant is critical for precise quantification of antioxidant phenolics and its further utilization in industry.

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