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

Mirta Resetar; Xin Liu; Sonja Herdlinger; Olaf Kunert; Eva-Maria Pferschy-Wenzig; Simone Latkolik; Theresa Steinacher; Daniela Schuster; Rudolf Bauer; Verena M. Dirsch

doi:10.1021/acs.jnatprod.9b00691

Titel

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

Autor*in

Mirta Resetar

Department für Pharmakognosie, Fakultät für Lebenswissenschaften, Universität Wien

Xin Liu

Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz

Sonja Herdlinger

Institute of Pharmacy, Pharmaceutical Chemistry, University of Innsbruck

... show all

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.

Stichwort

AlkylsAssaysChemical structureNoncovalent interactionsOrganic polymers

Objekt-Typ

journal article

Sprache

Englisch [eng]

Persistent identifier

phaidra.univie.ac.at/o:2093774

DOI

10.1021/acs.jnatprod.9b00691

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