1. Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.
- Author
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Wu, Sheng-Li, Zhang, Chen-Chen, Chen, Ji-Jun, Zhang, Xue-Mei, Guan, Min, and Geng, Chang-An
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VASOCONSTRICTORS , *MEDICINAL plants , *GLUCAGON-like peptide 1 , *CELL receptors , *NUCLEAR magnetic resonance spectroscopy , *STILBENE , *CELLULAR signal transduction , *SEEDS , *DESCRIPTIVE statistics , *TRANSFERASES , *PLANT extracts , *MOLECULAR structure , *MITOGEN-activated protein kinases , *COMPUTER-assisted molecular modeling , *PHARMACODYNAMICS , *CHEMICAL inhibitors - Abstract
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 μ M). 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 IP 3 , 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-IP 3 -Ca2+/CaMKII-MEK/ERK pathways. [Display omitted] • One usual stilbene trimer-flavonoid hybrid was isolated from peony seeds. • Six stilbenes showed stimulative effects on GLP-1 secretion. • Compounds 4 and 6 exhibited agonistic activity on TGR5 receptor. • The GLP-1 promotion of 6 was attenuated by IP 3 , Ca2+/CaMKII and MEK/ERK inhibitors. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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