Lignan Constituents from the Fruits of Viburnum macrocephalum f. keteleeri and Their α-Amylase, α-Glucosidase, and Protein Tyrosine Phosphatase 1B Inhibitory Activities

Abstract

Eight previously undescribed lignan glycosides, viburmacrosides A–H (1–8), and seven known analogues (9–15) were isolated from Viburnum macrocephalum f. keteleeri fruits through bioactivity-guided fractionation. Their structures and absolute configurations were elucidated by extensive spectroscopic analyses and chemical evidence. Using the well-recognized carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase, as well as the promising protein tyrosine phosphatase 1B (PTP1B), as inhibitory targets, all isolated compounds were tested for their antidiabetic potential in vitro. Compound 4 displayed potent inhibitory activities with IC50 values of 9.9 ± 0.6 and 8.9 ± 0.5 μM against α-glucosidase and PTP1B, respectively. The enzymatic kinetics results suggested that compound 4 competitively inhibited α-glucosidase while it suppressed α-amylase and PTP1B in the mixed-type manner. These findings supported that V. macrocephalum f. keteleeri fruits may be a new functional food resource with antidiabetic potential.

Natural α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitors: A Source of Scaffold Molecules for Synthesis of New Multitarget Antidiabetic Drugs

“…Compounds 18 – 24 and 41 – 48 have been isolated from Viburnum macrocephalum f . keteleeri [ 41 ]. Moreover, compounds 25 – 31 and 33 – 40 were extracted from the roots of Limonium gmelinii (Willd.)…”

“…Numerous lignans showing inhibitory activity toward both PTP1B and α-glucosidase have been recently isolated from various plants. Compounds 18-24 and 41-48 have been isolated from Viburnum macrocephalum f. keteleeri [41]. Moreover, compounds 25-31 and 33-40 were extracted from the roots of Limonium gmelinii (Willd.)…”

Recent Advance on Chemistry and Bioactivities of Secondary Metabolites from Viburnum Plants: An Update

“…In addition, the other epoxylignans including thirteen 2‐aryl‐4‐benzyltetrahydrofuran lignans ( 230 – 242 ) and one 2,5‐diaryltetrahydrofuran ( 243 ) were reported in Viburnum plants [31,53,55,56,61–63] . (+)‐9′‐ O ‐Senecioyllariciresinol ( 231 ) from V. odoratissmum var.…”

“…Lignans 246 – 268 containing the furofuran moiety were found in different Viburnum species ( Table 8, Figure 8). [9,50,56,59,63,64] Syringaresinol ( 252 ) and pinoresinol ( 253 ) from V. erosum exhibited considerable neuroprotective effects with EC 50 values of 6.33 and 6.96 μM by inhibiting the cell death of glutamate‐induced HT22 cells, as well as anti‐inflammatory activities with IC 50 values of 8.30 and 7.89 μM inhibiting NO production in LPS‐induced macrophage RAW 264.7 cells [56] . Compounds 254 , 255 , 266 and 267 displaying varying anti‐ α ‐glucosidase activity were obtained from the stems of Viburnum melanocarpum , among which, compound 267 showed stronger α ‐glucosidase inhibitory activity (IC 50 =10.3 μM) than the positive control acarbose (IC 50 =16.9 μM).…”

“…The SAR studies showed that the groups at C‐4/4′ might crucially influence the α ‐glucosidase inhibitory effect in the (7 S ,7′ S ,8 R ,8′ R )‐furofuran lignans. Compound 261 showed the strongest α ‐glucosidase inhibitory activity with the IC 50 value of 9.9 μM, and the most potent PTP1B inhibitory activity with the IC 50 value of 8.9 μM (ursolic acid, IC 50 =18.3 μM), which might ascribe to an apiofuranosyl group located at C‐2 of the glucopyranosyl moiety [63] …”