ch a response of interest is influenced by several variables, with the eventual objective of optimizing this response.[@bib0080] RSM has a major advantage over the one-factor-at-a time approach in that it allows for the evaluation of the effect of multiple variables and their interactions on the output variables with a lesser number of trials.[@bib0085] The optimization of the extraction process using RSM would not only serve as a visual aid to have a clearer picture about the effects of various factors on extraction but also help us to locate the region where the extraction is optimized.[@bib0090] In order to extract the bioactive compounds of the natural products, the RSM has been widely used in many studies.[@bib0095], [@bib0100], [@bib0105], [@bib0110], [@bib0115] For modeling, we used the central composite design (CCD) method for experimental design, and the results were fitted with a polynomial equation in the vicinity of the optimal condition.[@bib0120]

Therefore, the aim of the present study was to optimize variables of the ultrasound-assisted extraction method such as temperature, time, and concentration of methanol using response surface methodology, by employing central composite design to maximize the extraction of GA from licorice.

2. Methods {#sec0010}
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2.1. Plant material and reagents {#sec0015}
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The licorice used in this study was grown in China and purchased from an Oriental pharmacy in Geumsan, South Korea. It was authenticated by Dr. Goya Choi at the Korea Institute of Oriental Medicine (KIOM). Prior to extraction, the sample was pulverized using a disintegrator and then passed through a 600 μm sieve. A voucher specimen was deposited in the herbarium of the Herbal Medicine Resources Group at KIOM. The high performance liquid chromatography grade acetonitrile, methanol, ethanol, and distilled water were obtained from Burdick & Jackson (Muskegon, MI, USA). The analytical grade acetic acid was obtained from J. T. Baker Inc. (Phillipsburg, NJ, USA). T