| Summary: | Lychee seeds (LS) and longan seeds (LoS) are excellent sources of phenolic compounds (PCs) with strong antioxidant activity (AOA). The aim of this study was to optimize the extraction conditions regarding extraction yield (EY), extractable phenolic compound (EPC), and AOA from LS and LoS using surface response methodology (RSM). Solvent concentration, extraction temperature, time, and solid to liquid ratio were optimized using RSM. Increasing the solid to solvent ratio from 1:05 to 1:40 (<i>w</i>/<i>v</i>), increased EY for LoS, however, EY did not change from 1:20 to 1:40 for LS. Solid–liquid ratio 1:20 was chosen for this study. Increasing the quantity of solvent leads to higher EPC and FRAP. The results showed that LoS exhibited higher AOA than LS measured as DPPH, ABTS, and FRAP, respectively. Ethanol concentrations and temperatures significantly (<i>p <</i> 0.05) affect EY, EPC, and AOA. The results (<i>R</i><sup>2</sup> > 0.85) demonstrated a good fit to the suggested models and a strong correlation between the extraction conditions and the phenolic antioxidant responses. The ethanol concentrations of 41 and 53%, temperatures of 51 and 58 °C, and the corresponding times of 139 and 220 min were the optimal conditions that maximized the EY, EPC, and AOA from LS and LoS.
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