1. Academic Validation
  2. Sesquiterpenoids from Alpinia oxyphylla with GLP-1 Stimulative Effects through Ca2+/CaMKII and PKA Pathways and Multiple-Enzyme Inhibition

Sesquiterpenoids from Alpinia oxyphylla with GLP-1 Stimulative Effects through Ca2+/CaMKII and PKA Pathways and Multiple-Enzyme Inhibition

  • J Agric Food Chem. 2023 Oct 23. doi: 10.1021/acs.jafc.3c06093.
Can Cui 1 2 Sheng-Li Wu 2 Ji-Jun Chen 2 3 Pianchou Gongpan 2 Min Guan 4 Chang-An Geng 2
Affiliations

Affiliations

  • 1 College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, 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 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, People's Republic of China.
Abstract

Six new sesquiterpenoids (1-6), a pair of enantiomers (7a and 7b), and six known ones (8-13) were isolated from the fruits of Alpinia oxyphylla. The structures of the new compounds were elucidated by extensive spectroscopic data and ECD calculations. The stereochemistry of 7a and 7b was reported for the first time. All compounds showed significant GLP-1 stimulation in NCI-H716 cells with promoting ratios ranging from 90.4 to 668.9% at 50 μM. Mechanism study indicated that compound 6 stimulated GLP-1 secretion mainly by regulating the transcription and the shearing process of proglucagon, while compound 13 exerted its effects through up-regulating prkaca levels. Interestingly, the GLP-1 stimulative effects of 6 and 13 were both closely related with CA2+/CaMKII and PKA pathways but irrelevant to TGR5 and GPR119 receptors. Moreover, most compounds exhibited inhibitory activity against α-glucosidase and PTP1B at concentrations of 100 and 200 μM, while showing no activity against GPa. Compounds 3, 9, 11, and 13 could suppress α-glucosidase with IC50 values of 190.0, 204.0, 181.8, and 159.6 μM, equivalent to acarbose (IC50 = 212.0 μM). This study manifests that A. oxyphylla contains diverse sesquiterpenoids with multiple activities.

Keywords

Alpinia oxyphylla; Ca2+/CaMKII and PKA pathways; GLP-1 stimulation; sesquiterpenoids; α-glucosidase and PTP1B inhibitory activity.

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