Detailed investigation on the polyphenols from four Dendrobium species against α-glucosidase: An integrated in vitro and in silico approach

This work was aimed to investigate the α-glucosidase inhibitory potential of methanol, petroleum ether, ethyl acetate, n-butanol, and water extracts/fractions of four Dendrobium species, which are traditional medicinal plants over the centuries, and discovery some important polyphenols in terms of lowering blood sugar based our previous research. Furthermore, the enzyme kinetics, HPLC, fluorescence spectra, and molecular docking were performed to provide additional insights into the binding mechanisms between individual polyphenol and α-glucosidase. All the organic extracts/fractions showed promising results on α-glucosidase with IC50 values of 4.23–52.53 μg/mL. The EtOAcF of D. chrysotoxum (EtOAcF-DC) possessed the lowest IC50 value (4.23 ± 0.19 μg/mL) against α-glucosidase. And an obvious correlation existed between the total phenol contents and α-glucosidase inhition capacity. Schaftoside, isoschaftoside, 2,4,7-trihydroxy-9,10-dihydrophenanthrene (TD), dihydroresveratrol, coelonin, nudol (NU), gigantol (GT), erianin, and tristin were identified as the main polyphenol components in these four Dendrobium plants. However, only TD, NU, coelonin, and GT had significant inhibitory activity on α-glucosidase. TD, NU and GT were discovered simultaneously in the EtOAc fractions (EtOAcFs) of the four Dendrobium species and occupied higher contents than other components, thus being selected as objectives for deep research. The TD from Dendrobium species was first reported as α-glucosidase inhibitor with an IC50 value of 52.46 ± 2.34 μg/mL, which was almost 6.5 times stronger than that of acarbose (IC50 = 338.84 ± 18.57 μg/mL), signifying it was a potential candidate for treating diabetes. NU and GT acted as uncompetitive inhibitors against α-glucosidase, while TD and EtOAcF-DC exhibited mixed-type inhibition. The fluorescence spectra analysis demonstrated that these inhibitors could quenched the fluorescence spectrum of α-glucosidase significantly. Interestingly, the NU quenched fluorescence by an unusual static quenching method. The molecular simulation illustrated these three polyphenols interacted with α-glucosidase primarily through hydrogen bonds and van der Waals interactions, and the binding sites between polyphenols and α-glucosidase supported the obtained results of inhibition kinetics. This study revealed that the phenolic-rich extracts/fractions and polyphenol compounds from Dendrobium plants could be potential α-glucosidase inhibitors.