Identification of α-glucosidase inhibitors from Mulberry using UF-UPLC-QTOF-MS/MS and molecular docking

• Published in: Journal of functional foods Vol. 101; p. 105362
• Main Authors: Abudurexiti, Adalaiti, Zhang, Rui, Zhong, Yewei, Tan, Huiwen, Yan, Junlin, Bake, Subinuer, Ma, Xiaoli
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.02.2023
• Subjects: acarbose; active sites; animals; food plants; glycemic effect; HepG2 cells; insulin resistance; Molecular docking; mulberries; Mulberry; noninsulin-dependent diabetes mellitus; Oriental traditional medicine; spectroscopy; therapeutics; UF-UPLC-QTOF-MS/MS; α-glucosidase inhibitor; Mulberry; HepG2 cells; α-glucosidase inhibitor; UF-UPLC-QTOF-MS/MS; Molecular docking
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2022.105362

[Display omitted] •In this study, mulberry was used as a natural drug candidate for the screening of α-glucosidase inhibitory components of mulberry extracts by affinity ultrafiltration liquid mass spectrometry.•Molecular docking studies showed that these small molecules were more likely to occupy the active site of α-glucosidase than the positive control Acarbose, scoring above the threshold, suggesting that mulberry is a potential source of hypoglycaemic agents.•Cellular experiments revealed that the extracted parts and some monomeric compounds of Mulberry extract improved insulin resistance to some extent. As a medicinal and edible plant, Mulberry has shown good hypoglycaemic activity at the animal level, but its active ingredients and hypoglycaemic mechanisms remain unclear. In this study, we used ultrafiltration-ultra performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UF-UPLC-QTOF-MS/MS) and molecular docking to screen for high-affinity α-glucosidase inhibitors in Mulberry. Our innovation was to determine the inhibitory activity of Mulberry extracts in vitro and screen the active small molecules in the extracts using advanced UF-UPLC-QTOF-MS/MS techniques and validate these compounds at the molecular docking and cellular levels, laying the foundation for studying the mechanism of type 2 diabetes in Mulberry. α-Glucosidase incubation experiments showed that the IC50 value of Mulberry crude extracts was 37.58 μg/mL. Six possible α-glucosidase activity inhibitory components were identified using UF-UPLC-QTOF-MS/MS. Molecular docking studies showed that these small molecules were more likely to occupy the active site of α-glucosidase than the positive control acarbose, scoring above the threshold, indicating that Mulberry is a potential source of hypoglycemic agents. Further cellular level studies showed that different extracts and active small molecules of Mulberry improved insulin resistance in HepG2 cells. Through the analysis of glucose-lowering targeting components, the subject clarified that Mulberry exerts therapeutic effects on Diabetes Mellitus (DM) through a multi-component, multi-target, and multi-pathway relationship, which is consistent with Traditional Chinese Medicine (TCM) theory as a potential source of glucose-lowering agents.