Lignans with α-glucosidase, protein tyrosine phosphatase 1B, and aldose reductase inhibitory activities from the fruits of Viburnum cylindricum

Viburnum cylindricum Buch.-Ham. ex D. Don is widely cultivated in China due to its considerable economic value. In this study, the EtOAc fraction (VCFE) of V. cylindricum fruits (VCF) was first reported to obviously reduce postprandial blood glucose levels in normal and diabetic ICR mice at 100 mg/kg, and significantly inhibit α-glucosidase, PTP1B, and AR activities in vitro. In order to clarify its antidiabetic components, nine undescribed lignans, including seven 9,9′-epoxylignans, viburindrins A−G (1−7), one rare variable 9,9′-epoxylignan, viburindrin H (8), and one furofuran lignan, viburindrin I (9), were isolated from VCFE by bioassay-guided fractionation, and their structures including absolute configurations were identified by comprehensive spectroscopic analyses and the comparison of the experimental and calculated ECD spectra. Compounds 1−8 exhibited significant inhibitory activities against these enzymes. Among them, compounds 1, 4, and 8 possessed the most potent inhibitory effects on α-glucosidase, PTP1B, and AR with the IC50 values of 14.21, 6.14, and 1.08 μM, respectively. In addition, their inhibitory kinetics and molecular modeling analyses were also investigated. These results uncovered that VCF with the active lignans could be the potential resource for the improvement and treatment of diabetes and related complications.