In Vitro α-Glucosidase and Dipeptidyl Peptidase-IV Inhibitory Activities of Ethanol Extract and Its Fractions from the Leaves and Stems of Glehnia littoralis

This study evaluated the in vitro α-glucosidase and dipeptidyl peptidase-IV (DPP-IV) inhibitory and antioxidant activities of Glehnia littoralis leaves and stems, which are traditionally consumed but less studied than the roots. The 70% ethanol extract was partitioned into three fractions (F1, F2, F3). Fraction 2 (F2) concentrated total phenolics (234.71 mg GAE/g) and flavonoids (155.61 mg QE/g) most effectively, showing strong DPPH radical scavenging activity (IC50 = 32.09 µg/mL). F2 also demonstrated dual-targeting inhibitory efficacy against α-glucosidase (IC50 = 314.41 µg/mL) and DPP-IV (IC50 = 209.67 µg/mL), comparable to acarbose in α-glucosidase inhibition (yeast enzyme assay), though much less potent than sitagliptin against DPP-IV. Exploratory non-targeted metabolomics highlighted rutin and quercetin 3-β-D-glucoside (Q3G) as discriminating markers (VIP ≥ 2.0); their contents in F2, estimated by Parallel Reaction Monitoring, were 188.97 mg/g and 43.44 mg/g, respectively. In a concentration-addition analysis, the summed dose fractions of rutin, Q3G, and chlorogenic acid at the IC50 of F2 were approximately 0.32 and 0.62 for α-glucosidase and DPP-IV, respectively, suggesting contributions from additional, untested constituents such as kaempferol-3-O-rutinoside. These findings indicate that Glehnia littoralis leaves and stems merit further investigation as potential functional food resources for blood glucose regulation, pending cell-based and in vivo validation.