Anti-diabetic potential of Viburnum betulifolium fruits: Sesquilignans with α-amylase, α-glucosidase, and PTP1B inhibitory activities

Abstract

Viburnum betulifolium Batal. is an incredibly attractive and widely cultivated plant due to the great industrial value of its fruits, flowers, roots, stems, and barks. In this study, the MeOH extract of Viburnum betulifolium fruits (VBFM) was first reported to show obvious hypoglycemic effects in diabetic and normal mice, and it exhibited weak inhibitory effect on α-amylase and significant inhibition against α-glucosidase and PTP1B. In order to elucidate the anti-diabetic components, six undescribed sesquilignans, vibetulifols A−F (1−6), one new natural sesquilignan 9, and three known analogues (7, 8, and 10) were isolated from VBFM by bioactivity-guided fractionation and identified by extensive spectroscopic analyses. Compounds 1−8 exhibited moderate inhibitory effects on α-amylase with IC50 values ranging from 35.10 to 51.52 μM, and compounds 1−3 and 6 displayed significant α-glucosidase inhibitory effects (IC50 = 5.17, 6.73, 3.05, and 15.37 μM, respectively), while compounds 3 and 4 also displayed potent PTP1B inhibitory activities (IC50 = 3.29 and 3.15 μM, respectively) and good selectivity over TCPTP. Furthermore, the enzyme kinetic studies and molecular modeling analyses for compounds 3 and 4 were also performed. These results could provide scientific guidance and foundation for the further development and utilization of V. betulifolium fruits in pharmaceutical industry.