Polyacetylenes from Oplopanax horridus and Panax ginseng: Relationship between Structure and PPAR? Activation.

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 PPAR?, a ligand-activated transcription factor involved in metabolic regulation. Using a reporter gene assay, their potential was investigated to activate PPAR?. The majority of the polyacetylenes showed at least some PPAR? activity, among which oplopantriol B 18-acetate (1) and oplopantriol B (2) were the most potent partial PPAR? activators. By employing in silico molecular docking and comparing the activities of structural analogues, features are described that are involved in PPAR? 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 PPAR? 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 PPAR? partial agonists.

SUBMITTER: Resetar M 

PROVIDER: S-EPMC7187397 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature