Summary: | Extraction from edible plants is a highly important process that has various biological functions. To maximize biological activity, extraction methods should facilitate optimal extraction of functional phytochemicals. In this study, the optimal hydrothermal extraction conditions of <i>Acer tegmentosum</i> were determined using response surface methodology (RSM), and HepG2 cells were treated with optimized extract and hydrogen peroxide. In a central composition design, the independent variables were extraction temperature (X<sub>1</sub>: 70–90 °C), extraction time (X<sub>2</sub>: 2–6 h), and solvent-to-solid ratio (X<sub>3</sub>: 50–150). The maximum total phenolic contents (276.70 ± 10.11 mg GAE/g) and DPPH (2,2-diphenyl-1-pictylhydrazyl) activity (33.45 ± 2.20%) of <i>A. tegmentosum</i> were estimated at optimized extraction conditions, as follows: X<sub>1</sub>: 89.34 °C, X<sub>2</sub>: 7.36 h, X<sub>3</sub>: 184.09. Using the calculated extraction conditions, functional phytochemicals were extracted by hydrothermal extraction and freeze-dried. <i>A. tegmentosum</i> treatment (>10 μg/mL) of HepG2 cells remarkably attenuated hydrogen-peroxide-inducible hepatic cellular death and reactive oxygen species production in vitro.
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