Discovery of Natural α-Glucosidase Inhibitors from Hericium erinaceus Through Integrated Isolation, Structural Characterization, In Vitro Evaluation, and Molecular Dynamics Simulations.

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Citation abstract

Recognized for its dual nutritional and therapeutic value, the fungus Hericium erinaceus is increasingly acknowledged as a rich resource of naturally derived α -glucosidase inhibitors. In this study, eight compounds were isolated from H. erinaceus, including three novel compounds designated as erinacerins X-Z ( 1, 2, and 6 ). Their absolute configurations were definitively elucidated using a combination of NMR, HR-MS, and ECD calculations. Furthermore, an integrated screening strategy combining molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR) analysis identified two isoindolin-1-ones ( 2 and 3 ) as potent naturally derived α -glucosidase inhibitors. Notably, in vitro testing established compounds 2 and 3 as robust α -glucosidase inhibitors, affording IC 50 values of 17.80 ± 1.03 μM and 19.50 ± 1.33 μM, respectively. MD simulations revealed that electrostatic interactions and van der Waals forces are the primary drivers of this intermolecular association. These findings were further corroborated by SPR analysis, which quantified their high-affinity binding kinetics to the enzyme. Overall, this combined approach establishes a solid foundation for the discovery and development of natural α -glucosidase inhibitors from H. erinaceus.