Three new phenolic glycosides from root bark of Periploca sepium and their hypoglycemic activity.

Three new phenolic glycosides (1-3) and four known compounds were isolated from the ethanol extract of the root bark of Periploca sepium. Their chemical structures were elucidated based on comprehensive spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR) spectra. The sugar moieties were determined via acid hydrolysis followed by comparison with standard sugars. The hypoglycemic activity was evaluated by α-glucosidase and α-amylase inhibition assays. All four phenolic glycosides exhibited inhibitory activity against α-glucosidase and α-amylase with IC₅₀ values below 100 µM. Among them, compound 1 exhibited the strongest α-glucosidase inhibitory activity with an IC₅₀ value of 17.25 ± 1.39 µM, which was significantly better than that of the positive control acarbose (IC₅₀ = 111.2 ± 0.35 µM). Meanwhile, compound 2 showed the most potent α-amylase inhibitory activity with an IC₅₀ value of 30.99 ± 0.92 µM, also superior to acarbose (IC₅₀ = 149.63 ± 0.64 µM). Molecular docking results indicated that compounds 1-4 had strong binding affinity with α-glucosidase and α-amylase (ΔG < -6 kcal/mol), which further demonstrated that the four phenolic glycosides from P. sepium exerted their inhibitory effects on the two key enzymes through stable molecular binding interactions. These results suggested that the phenolic glycosides from P. sepium could be served as potential lead compounds for the development of anti-diabetic agents.