An Arylbenzofuran, Stilbene Dimers, and Prenylated Diels-Alder Adducts as Potent Diabetic Inhibitors from Morus bombycis Leaves

has a long history of usage as a treatment for metabolic diseases, especially, diabetes mellitus (DM). Thus, we aimed to isolate and evaluate bioactive constituents derived from leaves for the treatment of DM. According to bioassay-guided isolation by column chromatography, eight compounds were obtained from leaves: two phenolic compounds, -coumaric acid ( ) and chlorogenic acid methyl ester ( ), one stilbene, oxyresveratrol ( ), two stilbene dimers, macrourin B ( ) and austrafuran C ( ), one 2-arylbenzofuran, moracin M ( ), and two Diels-Alder type adducts, mulberrofuran F ( ) and chalcomoracin ( ). Among the eight isolated compounds, the anti-DM activity of - (which possess chemotaxonomic significance in Morus species) was evaluated by inhibition of α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation as well as by scavenging peroxynitrite (ONOO ), which are crucial therapeutic targets of DM and its complications. Compounds and - significantly inhibited α-glucosidase, PTP1B, and HRAR enzymes with mixed-type and non-competitive-type inhibition modes. Furthermore, the four compounds had low negative binding energies in both enzymes according to molecular docking simulation, and compounds - exhibited strong antioxidant capacity by inhibiting AGE formation and ONOO scavenging. Overall results suggested that the most active stilbene-dimer-type compounds ( and ) along with Diels-Alder type adducts ( and ) could be promising therapeutic and preventive resources against DM and have the potential to be used as antioxidants, anti-diabetic agents, and anti-diabetic complication agents.