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.