Bidirectional Modulation of α-Glucosidase by Steroidal Saponins From Polygonatum kingianum var. grandifolium: Inhibitory and Activating Effects Align With the Yin-Yang Balance Theory.

Three new steroidal saponins, kingianoside L-N (1-3), whose structures were elucidated through comprehensive spectroscopic analysis, and 15 known compounds (4-18) were isolated from Polygonatum kingianum var. grandifolium, a source of the traditional antihyperglycemic medicine Polygonati rhizome. The effects of compounds 1-13 on α-glucosidase activity were evaluated in vitro. Compound 4 exhibited stronger α-glucosidase inhibitory activity than the positive control acarbose, with a half-maximal inhibitory concentration of 213.9 µM, suggesting its potential as an inhibitor with hypoglycemic effects. Unexpectedly, compounds 1, 2, and 3 reversed dimethyl sulfoxide-suppressed α-glucosidase activity, with reactivation rates of 70.0%, 65.0%, and 61.1%, respectively, implying their possible value as activators for ameliorating functional degenerative disorders targeting α-glucosidase. These findings suggest that P. kingianum var. grandifolium exerts a dual regulatory effect on blood glucose levels through α-glucosidase inhibition and activation in diabetes management, aligning with the yin-yang balance theory in traditional Chinese medicine.