Optimization of Subcritical Water Extraction of Resveratrol from _Grape Seeds_ by Response Surface Methodology  
[PERSON]  
Beijing Key Laboratory of Lingucellulosic Chemistry, Beijing Forestry University, Beijing 100083, China; bjfu2017 [EMAIL_ADDRESS] (Y.T. ); [EMAIL_ADDRESS] (Y.W. ); [EMAIL_ADDRESS] (Y.M. ); [EMAIL_ADDRESS] (P.Z. );  
[PERSON]  
Beijing Key Laboratory of Lingucellulosic Chemistry, Beijing Forestry University, Beijing 100083, China; bjfu2017 [EMAIL_ADDRESS] (Y.T. ); [EMAIL_ADDRESS] (Y.W. ); [EMAIL_ADDRESS] (Y.M. ); m18810976557@163.  
gained significant worldwide attention due to its ability to inhibit or retard a wide variety of diseases in animals [10], including cardiovascular disease and cancer [11], and can increase stress resistance and lifespan. Thus, the extraction of resveratrol from grape seeds is meaningful work. Traditionally, resveratrol is extracted from natural products using organic solvents [12]. However, these techniques require long extraction times and result in low yields of extract. In recent years, some new techniques, such as extraction by supercritical fluids, extraction by pressurized liquids, and extraction assisted by microwave irradiation, have replaced conventional techniques like Soxhet extraction for solid samples [13]. These alternative techniques simplify the process, considerably reduce the consumption of solvents, and also increase the rate of the extraction process [14]. For example, [PERSON] gained resveratrol from the grape seeds, stems, skin, and pomace of the Palomino fino grape variety by supercritical carbon dioxide extraction. The best results were obtained by working at high pressure and low temperature using 5% \(\upsilon/v\) ethanol as a co-solvent [15]. [PERSON] extraction of trans-resveratrol from milled grape cases using a pressurized low-polarity water extractor. Increasing ethanol concentration from 0% to 25% increased the extraction of total phenolics by 44% [16]. Even though these techniques improve the extraction yield and reduce the extraction time, they still use conventional solvents (ethanol, methanol, etc.). These organic solvents are problematic in the extraction/separation of resveratrol from the herb because of their toxicity, volatility, and inflammability. Therefore, green technologies are needed. In addition, the effects of the various parameters on the extraction yield in the extraction process need to be further explored. The subcritical water, which is also called pressurized hot water or superheated water, is hot water that maintains in liquid state at temperatures between 100 and 374 \({}^{\circ}\)C under pressurized conditions. As a result of the breakdown of intermolecular hydrogen bonds, the dielectric constant of water decreases under subcritical conditions [17]. Modification of process parameters, such as temperature, affects the dielectric constant values and polarity. Water at room temperature has a high polarity and dielectric constant close to 80. The application of suitable pressure in order to keep water in liquid form at 250 \({}^{\circ}\)C leads to a decrease of the dielectric constant to 27, which is similar to that of ethanol [18]. The subcritical water extraction has shown its capability to selectively extract various groups of compounds by adjusting temperatures. At lower temperatures, more polar compounds are extracted, while higher temperatures are used for extraction of less polar compounds [19]. So far, subcritical water extraction has been shown to be a promising alternative for the conventional method for the extraction of polar and slightly non-polar compounds [20]. In this work, we reported the extraction of resveratrol from grape seeds by subcritical water extraction technique. This method can effectively extract the resveratrol from grape seeds without any organic solvent. In addition, the other main objective of this work was to investigate the influence of process parameters (pressure, temperature, time, and solid/solvent ratio) on resveratrol extraction yield from grape seeds.