This research was conducted for the purpose of extracting flavonoids and terpenoids from perilla leaves (Perilla frutescens var. crispa) using high-speed-shearing-enzymatic-assisted extraction (HSSEAE) in combination with natural deep eutectic solvents (NADES). Various solvents were examined to select the most suitable for further extraction experiments. The one-factor experiment was employed to investigate the influence of different parameters of HSSEAE on the efficacy of flavonoid and terpenoid extraction from perilla leaves. The Plackett–Burman Design Model was used to evaluate the significance of independent variables on the dependent responses in the optimal condition ranges. The Box-Behnken Design Model was employed to determine the optimal extracting conditions for obtaining bioactive compounds from perilla leaves. The highest yield of total flavonoid contents (TFC) and total terpenoid contents (TTC) using HSSEAE was 40.37 ± 1.02 mg rutin acid equivalent per gram of dry weight (mg RE/g dw) and 37.93 ± 1.59 mg ursolic acid equivalent per gram of dry weight (mg UE/g dw), respectively. Meanwhile, the traditional extraction (TrE) process using acidified ethanol as solvent yielded lower results: TFC: 8.7 ± 0.17 mg RE/g dw; and TTC: 8.04 ± 0.55 mg UE/g dw. The second-order extraction kinetics model was used to figure out the principle of the HSSEAE process. Scanning electron microscope and X-ray diffraction were employed to indicate the surface morphology crystallinity of perilla leaves before and after HSSEAE. This extraction approach can be considered highly effective and sustainable for the recovery process of bioactive compounds originating from plants.
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