Inhibitory effects of flavonoids and alkaloids from the traditional antihyperglycemic herb Polygonatum kingianum var. grandifolium on α-glucosidase activity

The rhizome of Polygonatum kingianum var. grandifolium (commercially used as Polygonati rhizoma) yielded three new compounds: 8-methylaromadendrin (1), N-p-coumaroyl-7-butoxytyramine (2), and N-cis-p-coumaroyl-7-ethoxytyramine (3), alongside 23 known compounds (4–26). Specifically, compound 2 was separated into four isomers (2a-2d) with cis/trans and 7 R/7S configurations confirmed by coupling constants and Cotton effects, and compounds 4–16, 20, 21, 24, and 26 were identified in this herb for the first time. All isolates were screened for in vitro inhibitory effects on α-glucosidase. Notably, alkaloids 5, 6/7 (tested as a mixture), and 12, along with flavonoids 20, and 23–25, demonstrated significant inhibition, with IC50 values between 2.5 and 51.3 μM, suggesting promising potential as α-glucosidase inhibitors. Moreover, compounds 1, 2, 4, 8, 11, 13, 17–19, 21, and 22 exhibited moderate inhibition with IC50 values spanning 104.8–646.5 μM. These alkaloids and flavonoids may explain how P. kingianum var. grandifolium aids in preventing and treating T2DM.