A mechanochemical pretreatment (MCPT) was applied to aqueous extraction of isofraxidin from the Asian herb Eleutherococcus senticosus. Six extraction variables (Na2CO3 content, particle size, solvent, extraction time, liquid/solid ratio, and extraction temperature) were varied in order to optimize extraction efficiency. Optimal extraction was obtained using superfine powdered plant material (D-95 <= 44,rho m) with Na2CO3 content of 2.0% (w/w) and extraction with water (liquid/solid ratio of 20: 1, mL/g) for 5 min at 25 degrees C. The efficiency of mechanochemical-assisted extraction (MCAE) of isofraxidin was compared to that of heat-reflux and superfine grinding extraction. With the optimized parameter settings, MCAE with water as solvent gave the highest isofraxidin yield while reducing both extraction time and energy costs compared to the conventional methods.