Bio-Assay Guided Isolation of Flavonoids from Scutellaria barbata D. Don and Their Mechanism of [alpha]-Glucosidase Inhibition

• Published in: Pharmaceutical chemistry journal 2022-08, Vol.56 (5), p.683
• Main Authors: Dlamini, Bongani Sicelo, Chen, Chiy-Rong, Kuo, Yueh-Hsiung, Chen, Yu-Kuo, Hsu, Jue-Liang, Chang, Chi-I
• Format: Article
• Language: English
• Subjects: Blood sugar; Chromatography; Enzymes; Health aspects; Hydrogen; Hydrolases; Isoflavones; Nuclear magnetic resonance; Sugars
• ISSN: 0091-150X
• DOI: 10.1007/s11094-022-02695-y

Inhibition of [alpha]-glucosidase is a therapeutic approach that slows down the hydrolysis of oligosaccharides and disaccharides to glucose. Therefore, delaying the digestion and absorption of carbohydrates by inhibiting [alpha]-glucosidase can reduce blood glucose levels. Herein, the methanol extract of Scutellaria barbata D. Don was screened for [alpha]-glucosidase inhibitors using an in vitro inhibition assay and chromatographic techniques (column chromatography, TLC, and HPLC). Six known flavonoids were isolated, including chrysin (1), wogonin (2), apigenin (3), hispidulin (4), pinocembrin (5) and 6-methoxyaringenin (6), and their structures were identified by spectroscopic methods (NMR and MS) and by comparing their spectral data to reported values. Compounds 1 - 6 exhibited higher inhibitory activities against [alpha]-glucosidase with IC.sub.50 values between 17 [mu]M and 192 [mu]M compared to the reference drug acarbose (1463.0 ± 29.5 [mu]M). The kinetic analysis showed that flavonoid 1 was a competitive inhibitor, flavonoids 2 and 4 were mixed-type inhibitors, while flavonoids 3, 5 and 6 were noncompetitive inhibitors of [alpha]-glucosidase. Computer modeling showed that the primary amino acid residue interacted with the flavonoids primarily through hydrogen bonding, with binding energies ranging from -5.44 to -1.85 kcal/mol. These results indicate that compounds 1 - 6 are potential [alpha]-glucosidase inhibitors.