Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α]D spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.8%-880.4% (25 µM) and 217.6%-1089.4% (50 µM), more potent than the positive control, oleoylethanolamide (250.2% at 50 µM). Moreover, compounds 4 and 6 exhibited agonistic activity on the G protein-coupled receptor (GPCR) TGR5 with stimulative ratios of 40.2% and 40.5% at 50 µM, and 54.2% and 49.1% at 100 µM, respectively. Docking study manifested that 6 well located in the catalytic pocket of TGR5 by hydrogen-bond and hydrophobic interactions. The GLP-1 promotion of 6 could be attenuated by IP3, Ca2+/CaMKII and MEK/ERK pathway inhibitors, suggesting that these pathways played important roles in GLP-1 secretion. Thus, stilbenes in peony seeds maybe regarded as potential GLP-1 secretagogues through TGR5-IP3-Ca2+/CaMKII-MEK/ERK pathways.

Antidiabetic Stilbenes from Peony Seeds with PTP1B, α-Glucosidase, and DPPIV Inhibitory Activities.

One unusual resveratrol tetramer, paeonilactiflorol (1), and 14 known compounds (2-15) were isolated from peony seeds ( Paeonia lactiflora) under the guidance of bioassay. Paeonilactiflorol (1) was determined by extensive HRESIMS, UV, IR, 1D and 2D NMR spectroscopic analyses. Most of the stilbenes showed obvious inhibition on PTP1B and α-glucosidase, superior to the monoterpene glycosides. Especially, the stilbene tetramer (1) and trimer (8) exhibited high activity inhibiting both PTP1B with IC50 values of 27.23 and 27.81 µM and α-glucosidase with IC50 values of 13.57 and 14.39 µM. Two trans-dimers (4 and 5) also showed dipeptidyl peptidase-4 (DPPIV) inhibitory activity (55.35% and 61.26%, 500 µM) in addition to PTP1B and α-glucosidase. Enzyme kinetic study indicated that the types of inhibition on PTP1B were noncompetitive for 3 and 5 and mixed for 8 and 10. Quantitative analysis suggested that the stilbene trimers 8 (23.17 ± 0.36 mg/g) and 10 (15.24 ± 0.25 mg/g) were the main contents in peony seeds and should be responsible for the antidiabetic effects. This investigation supports the therapeutic potential of peony seeds in the treatment of diabetes with stilbenes as the active constituents.

Simultaneous determination of four alkaloids in Solanum lyratum Thunb by UPLC-MS/MS method.

Four alkaloids, strychnine, soladulcidine, solamargine and (3-O-beta-D-glucopyranosyl-(1 --> 2)beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside-(25xi)-solanidan-3beta,23beta-diol)(abbreviation, glycoalkaloid A) were isolated from Solanum lyratum Thunb. The structures were elucidated by NMR and measuring physicochemical properties. Then a novel and rapid method using an ultra-performance liquid chromatography coupled with mass spectrometry was developed and validated for the simultaneous determination of these compounds. An acquit UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was used. Acetonitrile and 0.1% formic acid were adopted as mobile phase. Detection was performed on a Waters Micromass Quattro Premier tandem quadrupole mass spectrometer in the positive ion mode using an electrospray source. The multiple reaction monitoring (MRM) mode was used to detect the target compounds. The established method showed a good linearity (R2 > 0.999 0) over the investigated concentration ranges, good inter-day and intra-day precisions (less than 2%) and good recoveries (from 99.8% to 100.1%) for all four target compounds. Compared to previous methods employing conventional high performance liquid chromatography (HPLC) separation, the ultra-high-pressure liquid chromatography-tandem mass spectrometry achieved preferable chromatographic parameters and significantly increased sample throughput.