PUBLICATION
(+)/(-)-Gerbeloid A, a pair of unprecedented coumarin-based polycyclic meroterpenoid enantiomers from Gerbera piloselloides: Structural elucidation, semi-synthesis, and lipid-lowering activity
- Authors
- Zhao, C., Li, J., Hu, Y., Li, L., Yu, M., Huang, Y., Zhang, T., Shang, H., Zou, Z.
- ID
- ZDB-PUB-240603-9
- Date
- 2024
- Source
- Acta pharmaceutica Sinica. B 14: 265726682657-2668 (Journal)
- Registered Authors
- Keywords
- 3T3-L1 adipocytes, Biomimetic synthesis, Coumarin meroterpenoid, Gerbera piloselloides, High-fat diet zebrafish model, Lipid-lowering activity, Natural products, Structural elucidation
- MeSH Terms
- none
- PubMed
- 38828137 Full text @ Acta Pharm Sin B
Citation
Zhao, C., Li, J., Hu, Y., Li, L., Yu, M., Huang, Y., Zhang, T., Shang, H., Zou, Z. (2024) (+)/(-)-Gerbeloid A, a pair of unprecedented coumarin-based polycyclic meroterpenoid enantiomers from Gerbera piloselloides: Structural elucidation, semi-synthesis, and lipid-lowering activity. Acta pharmaceutica Sinica. B. 14:265726682657-2668.
Abstract
A pair of coumarin-based polycyclic meroterpenoid enantiomers (+)/(-)-gerbeloid A [(+)-1a and (-)-1b] were isolated from the medicinal plant Gerbera piloselloides, which have a unique caged oxatricyclo [4.2.2.03,8] decene scaffold. Their planar and three-dimensional structures were exhaustively characterized by comprehensive spectroscopic data and X-ray diffraction analysis. Guided by the hypothetical biosynthetic pathway, the biomimetic synthesis of racemic 1 was achieved using 4-hydroxy-5-methylcoumarin and citral as the starting material via oxa-6π electrocyclization and intramolecular [2 + 2] photocycloaddition. Subsequently, the results of the biological activity assay demonstrated that both (+)-1a and (-)-1b exhibited potent lipid-lowering effects in 3T3-L1 adipocytes and the high-fat diet zebrafish model. Notably, the lipid-lowering activity of (+)-1a is better than that of (-)-1b at the same concentration, and molecular mechanism study has shown that (+)-1a and (-)-1b impairs adipocyte differentiation and stimulate lipolysis by regulating C/EBPα/PPARγ signaling and Perilipin signaling in vitro and in vivo. Our findings provide a promising drug model molecule for the treatment of obesity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping