| Summary: | Gout is an oxidative stress-related disease. Food-derived vanillic acid, a promising xanthine oxidase inhibitor, could potentially be used as a safe, supportive, and therapeutic product for gout. The extraction of vanillic acid from a classic Chinese herbal plant <i>Amomum villosum</i> with ethanol was investigated in the study. The optimum conditions were determined as extraction time of 74 min, extraction temperature of 48.36 °C, and a solid-to-liquid ratio of 1:35 g·mL<sup>−1</sup> using the Box–Behnken design (BBD) of response surface methodology (RSM). The experimental extraction yield of 9.276 mg·g<sup>−1</sup> matched with the theoretical value of 9.272 ± 0.011 mg·g<sup>−1</sup> predicted by the model. The vanillic acid in <i>Amomum villosum</i> was determined to be 0.5450 mg·g<sup>−1</sup> by high-performance liquid chromatography–diode array detection (HPLC–DAD) under the optimum extraction conditions and exhibited xanthine oxidase (XO) inhibitory activity, with the half-maximal inhibitory concentration (IC50) of 1.762 mg·mL<sup>−1</sup>. The nanoemulsion of <i>Amomum villosum</i> extract consists of 49.97% distilled water, 35.09% <i>S<sub>mix</sub></i> (mixture of tween 80 and 95% ethanol with 2:1 ratio), and 14.94% n-octanol, with a particle size of 110.3 ± 1.9 nm. The nanoemulsion of <i>Amomum villosum</i> extract exhibited markable XO inhibitory activity, with an inhibition rate of 58.71%. The result demonstrated the potential benefit of <i>Amomum villosum</i> as an important dietary source of xanthine oxidase inhibitors for gout.
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