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

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

  • Fitoterapia. 2022 Oct 15;105336. doi: 10.1016/j.fitote.2022.105336.
Sheng-Li Wu 1,  Chen-Chen Zhang 2,  Ji-Jun Chen 3,  Xue-Mei Zhang 2,  Min Guan 4,  Chang-An Geng 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; School of Life Sciences, Yunnan University, Kunming 650500, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
  • 4 Center for Human Tissues and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • 5 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China. Electronic address: gengchangan@mail.kib.ac.cn.
PMID: 36257378 DOI: 10.1016/j.fitote.2022.105336
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 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.

Keywords

GLP-1 secretagogues; Paeonia lactiflora; Paeonilactiflobenoid; Stilbene trimer-flavonoid hybrid; Stilbenes.

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