Bioassay-guided isolation of α-Glucosidase inhibitory constituents from Hypericum sampsonii

This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties.Hypericum sampsonii was investigated,leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols(PPAPs)(1 and 2),eight phenolic derivatives(3-10),and four terpene derivatives(11-14).The structures of compounds 1 and 2,featuring an unprecedented octahydro-2H-chromen-2-one ring system,were fully characterized using extensive spectroscopic data and quantum chemistry calculations.Six compounds(1,5-7,9,and 14)exhibited potential inhibitory effects against α-glucosidase,with IC_(50) values ranging from 0.050±0.0016 to 366.70±11.08μg·mL^(-1).Notably,compound 5(0.050±0.0016μg·mL^(-1))was identified as the most potential α-glucosidase inhibitor,with an inhibitory effect about 6900 times stronger than the positive control,acarbose(IC_(50)=346.63±15.65μg·mL^(-1)).A docking study was conducted to predict molecular interactions between two compounds(1 and 5)and α-glucosidase,and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.