Facilitated Visual Interpretation of Scores in Principal Component Analysis by Bioactivity-Labeling of (1)H-NMR Spectra—Metabolomics Investigation and Identification of a New α-Glucosidase Inhibitor in Radix Astragali

Radix Astragali is a component of several traditional medicines used for the treatment of type 2 diabetes in China. Radix Astragali is known to contain isoflavones, which inhibit α-glucosidase in the small intestines, and thus lowers the blood glucose levels. In this study, 21 samples obtained from different regions of China were extracted with ethyl acetate, then the IC(50)-values were determined, and the crude extracts were analyzed by (1)H-NMR spectroscopy. A principal component analysis of the (1)H-NMR spectra labeled with their IC(50)-values, that is, bioactivity-labeled (1)H-NMR spectra, showed a clear correlation between spectral profiles and the α-glucosidase inhibitory activity. The loading plot and LC-HRMS/NMR of microfractions indicated that previously unknown long chain ferulates could be partly responsible for the observed antidiabetic activity of Radix Astragali. Subsequent preparative scale isolation revealed a compound not previously reported, linoleyl ferulate (1), showing α-glucosidase inhibitory activity (IC(50) 0.5 mM) at a level comparable to the previously studied isoflavones. A closely related analogue, hexadecyl ferulate (2), did not show significant inhibitory activity, and the double bonds in the alcohol part of 1 seem to be important structural features for the α-glucosidase inhibitory activity. This proof of concept study demonstrates that bioactivity-labeling of the (1)H-NMR spectral data of crude extracts allows global and nonselective identification of individual constituents contributing to the crude extract’s bioactivity.