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Polyacetylenes from Oplopanax horridus and Panax ginseng: Relationship between Structure and PPARγ Activation

Authors
  • Resetar, Mirta1
  • Liu, Xin2
  • Herdlinger, Sonja3
  • Kunert, Olaf2
  • Pferschy-Wenzig, Eva-Maria2
  • Latkolik, Simone1
  • Steinacher, Theresa3
  • Schuster, Daniela4
  • Bauer, Rudolf2
  • Dirsch, Verena M.1
  • 1 University of Vienna, Austria , (Austria)
  • 2 University of Graz, Austria , (Austria)
  • 3 University of Innsbruck, Austria , (Austria)
  • 4 Paracelsus Medical University, Austria , (Austria)
Type
Published Article
Journal
Journal of Natural Products
Publisher
American Chemical Society
Publication Date
Mar 04, 2020
Volume
83
Issue
4
Pages
918–926
Identifiers
DOI: 10.1021/acs.jnatprod.9b00691
PMID: 32129622
PMCID: PMC7187397
Source
PubMed Central
License
Unknown

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.

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