Ionic liquid-assisted extraction can improve the recovery of monoterpene glycosides from Radix Paeoniae Alba, whereas post-extraction purification and ionic-liquid-associated marker-level quality control remain necessary before further bioactivity evaluation. In this study, a macroporous resin-based purification process was developed for monoterpene glycoside-enriched extracts obtained by conventional reflux extraction and ionic liquid-assisted microwave–ultrasound extraction. Among the five tested resins, AB-8 resin showed the best adsorption performance and was selected for further process optimization. The optimized purification conditions were a loading concentration of 13 mg/mL, loading pH of 7, elution with 70% ethanol, loading volume of 6 BV and elution volume of 9 BV. After purification, the total quantified monoterpene glycoside content increased from 6.59% to 51.68% in the conventional extract and from 15.30% to 75.30% in the ionic liquid-assisted extract. The ionic-liquid-associated elemental marker content in the ionic liquid-assisted extract decreased from 5.593% to 0.072% after purification, corresponding to an approximately 98.7% reduction at the elemental-marker level. Stability evaluation indicated that Na₂SO₃, Fe³⁺, ascorbic acid, sucrose and light exposure affected the detected monoterpene glycoside content to different extents, whereas short-term heating within 20–80 °C caused only slight fluctuations. The purified extracts showed stronger DPPH and ABTS radical scavenging activities and reducing power than the crude extracts. In LPS-stimulated RAW264.7 cells, the purified extracts reduced NO production and downregulated the mRNA expression of IL-6, IL-1β, TNF-α, iNOS and COX-2, suggesting anti-inflammatory potential at the NO and gene-expression levels. AB-8 resin purification enriched the monitored monoterpene glycosides, reduced the selected ionic-liquid-associated elemental marker, and generated purified fractions suitable for subsequent stability and bioactivity evaluation.

Radix Paeoniae Alba, the dried root of Paeonia lactiflora Pall., contains characteristic monoterpene glycosides, but efficient recovery of these polar constituents remains challenging. This study developed an ionic liquid-assisted sequential ultrasound–microwave extraction method and evaluated paeoniflorin, oxypaeoniflorin and albiflorin by HPLC as multi-marker responses. Among the ionic liquids tested, 1-propyl-3-methylimidazolium dihydrogen phosphate showed the best extraction response. Box–Behnken response surface optimization gave practical extraction conditions of a solid-to-liquid ratio of 1:26 g/mL, ionic liquid concentration of 0.12 mol/L and ultrasound time of 22 min. Under these conditions, paeoniflorin and total marker glycosides reached 29.12 and 34.98 mg/g dry material, respectively, representing increases of 32.4% and 34.5% compared with conventional reflux extraction. UPLC-QTOF-MS profiling provided complementary chemical profile information for the optimized extract and tentatively annotated Paeonia-related monoterpene glycoside derivatives, galloylated glucose derivatives and polyphenolic constituents. Electrostatic potential, SAPT and non-covalent interaction analyses, supported by ¹H NMR chemical shift perturbation, suggested possible hydrogen bonding, electrostatic and dispersion interactions between paeoniflorin and the selected ionic liquid. These results support the optimized process as an efficient extraction approach and provide molecular interaction insights into ionic liquid-assisted recovery of monoterpene glycosides.