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Polyacetylenes from Oplopanax horridus and Panax ginseng: Relationship between Structure and PPARγ Activation
- Source :
- Journal of Natural Products
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- Oplopanax horridus and Panax ginseng are members of the plant family Araliaceae, which is rich in structurally diverse polyacetylenes. In this work, we isolated and determined structures of 23 aliphatic C17 and C18 polyacetylenes, of which five are new compounds. Polyacetylenes have a suitable scaffold for binding to PPARγ, a ligand-activated transcription factor involved in metabolic regulation. Using a reporter gene assay, their potential was investigated to activate PPARγ. The majority of the polyacetylenes showed at least some PPARγ activity, among which oplopantriol B 18-acetate (1) and oplopantriol B (2) were the most potent partial PPARγ activators. By employing in silico molecular docking and comparing the activities of structural analogues, features are described that are involved in PPARγ activation, as well as in cytotoxicity. It was found that the type of C-1 to C-2 bond, the polarity of the terminal alkyl chain, and the backbone flexibility can impact bioactivity of polyacetylenes, while diol structures with a C-1 to C-2 double bond showed enhanced cytotoxicity. Since PPARγ activators have antidiabetic and anti-inflammatory properties, the present results may help explain some of the beneficial effects observed in the traditional use of O. horridus extracts. Additionally, they might guide the polyacetylene-based design of future PPARγ partial agonists.
- Subjects :
- Models, Molecular
Stereochemistry
In silico
Diol
Panax
Pharmaceutical Science
Plant Roots
01 natural sciences
Article
Analytical Chemistry
Structure-Activity Relationship
Ginseng
chemistry.chemical_compound
Drug Discovery
Humans
Hypoglycemic Agents
Cytotoxicity
Transcription factor
Oplopanax
Pharmacology
Reporter gene
Molecular Structure
biology
Plant Extracts
010405 organic chemistry
Chemistry
Anti-Inflammatory Agents, Non-Steroidal
Organic Chemistry
Polyynes
biology.organism_classification
0104 chemical sciences
Molecular Docking Simulation
PPAR gamma
010404 medicinal & biomolecular chemistry
HEK293 Cells
Complementary and alternative medicine
Molecular Medicine
Araliaceae
Subjects
Details
- ISSN :
- 15206025 and 01633864
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- Journal of Natural Products
- Accession number :
- edsair.doi.dedup.....2b45bbe65c4abee26aa33f14619b874c