Ultrasonic Extraction, Metabolomic Analysis and Antioxidant Activities of Phenylethanoid Glycosides in Cistanche deserticola

The aim of this study was to optimize the ultrasound-assisted extraction (UAE) process of Phenylethanoid Glycosides (PhGs) from Cistanche deserticola and to elucidate the mechanism of bioactivity enhancement from a metabolomic perspective. A sequential optimization strategy was employed, combining single-factor experiments, Plackett-Burman design (PBD) to screen for significant variables, and Box-Behnken design (BBD) for response surface methodology (RSM). The optimal extraction parameters, which were the liquid-solid ratio of 14:1   v/w, the ultrasonic power of 215   W, and the ethanol concentration of 55%, which resulted in the yield of PhGs of 122.51±5.07   mg/g. Metabolomics analysis by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-ESI-MS/MS) revealed that the content of phenolic acids, flavonoids and terpenoids in the ultrasound-assisted ethanol extract (EEC) was significantly higher than that of the traditional solvent-extracted ethanol extract (ESC) ( p < 0.05), and the antioxidant capacity (DPPH IC 50 =57.79   μg/mL, ABTS IC 50 =51.56   μg/mL, FRAP = 0.74   mg FeSO 4 /g) were significantly better than that of ESC. Principal component analysis (PCA) confirmed a strong correlation between the enrichment of these bioactive constituents and the enhanced functional activities. This study reveals for the first time that ultrasound-assisted extraction enhances the antioxidant and anti-inflammatory potentials of C. deserticola extracts through selective enrichment of phenolic acids, flavonoids, and terpenoids compared to conventional extraction by metabolomics, which provides a theoretical basis for the highly efficient extraction of active ingredients of plant origin and the application of C. deserticola in the development of functional foods.