Optimization of ultrasonic-assisted extraction (UAE) of phenolic and antioxidant compounds from Ephedra foeminea Forssk. using response surface methodology (RSM)

Ephedra foeminea Forssk., a Mediterranean shrub with diverse traditional medicinal applications, is rich in bioactive metabolites [ 1 ] [ 2 ]. This study optimized the ultrasonic-assisted extraction (UAE) of phenolic and antioxidant compounds from E. foeminea using response surface methodology (RSM). A circumscribed central composite design was applied to assess the influence of four variables—solvent volume (20-40 mL/g), ethanol concentration (50-70%), sonication time (10-20 min), and temperature (35-45°C)—on extraction yield (Y%), total phenolic content (TPC), and radical scavenging activity (RSA%). The enhanced statistical models provided the following optimal conditions for each output: Y% (11.93±0.09%) at V=28.2 mL/g, E=67.9%, S=19.1 min, T=39.3°C; TPC (3.06±0.06 mg GAE/g) at V=32.6 mL/g, E=65.1%, S=17.3 min, T=40.5°C; and RSA% (90.63±1.08%) at V=31.8 mL/g, E=66.7%, S=19.7 min, T=40.5°C. High-performance liquid chromatography (HPLC) confirmed that the RSM-optimized UAE conditions enriched phenolics, including gallic acid, luteolin, and apigenin [ 3 ]. Principal component analysis (PCA) showed strong correlations between TPC and RSA%, with PC1 and PC2 explaining 98.0% of the variance. These findings establish RSM-optimized UAE as a potent method for extracting antioxidant-rich phenolics from E. foeminea , supporting its potential use in functional and therapeutic applications [ 4 ], 5 ([ Fig. 1 ]). Fig. 1 A graphical abstract of the optimization of ultrasonic-assisted extraction (UAE) of phenolic and antioxidant compounds from E. foeminea using response surface methodology (RSM). Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany