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A microwave-assisted extraction (MAE) method was applied to separate saponins from Sapindus mukorossi pericarps. The most important factors of the six extraction parameters were selected using Plackett–Burman designs; therefore, the further extraction procedure was optimized using the Box–Behnken designs; meanwhile, the optimum processing parameters and well-pleasing saponins extraction rate were inferred. The final operation conditions were the ethanol concentration of 40%, soaking time of 3 h, particle size of 80–100 meshes, extraction time of 13 min, solvent-solid ratio of 19 mL/g, and microwave power of 425 W. Based on the optimal extraction parameters, the extraction rate of the saponins by means of MAE technique reached 280.55 ± 6.81 mg/g, which exceeds yields acquired using conventional manners. Saponins from S. mukorossi have obvious xanthine oxidase inhibitory properties in vitro compared with allopurinol. The saponins displayed a type of competitive inhibition of xanthine oxidase. In conclusion, a MAE technique in association with a response surface design provides an efficient extraction tactics, which could sufficiently isolate saponins from S. mukorossi pericarps; further, this technique could be applied to the dissociation of other bioactive substances from plant sources. In addition, the saponins may be a promising alternative to conventional medicine to treat gout and other inflammation-associated disorders to mitigate the side effects of traditional drugs.

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