Structurally Diverse Stilbenoids as Potent α‑Glucosidase Inhibitors with Antidiabetic Effect from Morus alba

• Published in: Journal of agricultural and food chemistry Vol. 72; no. 32; pp. 17938 - 17952
• Main Authors: Tian, Lin-Lin, Bi, Yan-Xue, Zhang, Hua
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 14.08.2024; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; Bioactive Constituents, Metabolites, and Functions; Chemistry; Chemistry, Applied; Food Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Science & Technology; antihyperglycemia; stilbenoid; albaphenol; antidiabetic; α-glucosidase inhibitor; Morus alba; alpha-glucosidase inhibitor; ALDER-TYPE ADDUCTS; L; CULTIVATED MULBERRY TREE; PTP1B; ROOT BARK; MEDICINAL-PLANTS; DERIVATIVES; CONSTITUENTS
• ISSN: 0021-8561; 1520-5118; 1520-5118
• DOI: 10.1021/acs.jafc.4c01681

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A–E, 1–5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro­[bicyclo[3.2.1]­octane-6,3′-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70–8.27 μM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.