Involvement of the Glucocorticoid Receptor in Pro-inflammatory Transcription Factor Inhibition by Daucane Esters from Laserpitium zernyi

Species of the genus Laserpitium have been used traditionally to treat inflammation and infection. From the herb of Laserpitium zernyi, six new compounds were isolated and their structures elucidated (using IR, NMR, HRMS data) as derivatives of 8-daucene-2,4,10-triol (1, 2, and 4), 7-daucene-2,4,10-...

Full description

Saved in:
Bibliographic Details
Published inJournal of natural products (Washington, D.C.) Vol. 80; no. 5; pp. 1505 - 1513
Main Authors Popović, Višnja, Goeman, Jan L, Bougarne, Nadia, Eyckerman, Sven, Heyerick, Arne, De Bosscher, Karolien, Van der Eycken, Johan
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society and American Society of Pharmacognosy 26.05.2017
Amer Chemical Soc
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary:Species of the genus Laserpitium have been used traditionally to treat inflammation and infection. From the herb of Laserpitium zernyi, six new compounds were isolated and their structures elucidated (using IR, NMR, HRMS data) as derivatives of 8-daucene-2,4,10-triol (1, 2, and 4), 7-daucene-2,4,10-triol (3), a lapiferin derivative featuring a C-2 ester moiety (5), and a daucane featuring an exomethylene group at C-8 (6). Also isolated were the rare daucanes vaginatin (7) and laserpitin (8). In a search for selective glucocorticoid receptor (GR) modulators, the compounds were tested for their capacity to inhibit NF-κB and AP-1 pro-inflammatory factors and for a potential competitive effect on a dexamethasone (Dex)-induced GR-driven glucocorticoid response element (GRE) reporter gene. The new 2β-angeloyloxy-10α-acetoxy-8-daucene-2,4,10-triol (2) significantly inhibited transactivation of both NF-κB and AP-1, while vaginatin (7) was the most active of the compounds tested in blocking AP-1. Both compounds competitively repressed Dex-induced GRE-driven promoter activities, indicative of a potential role for GR. In addition, a decreased potential to inhibit NF-κB was apparent in GR knockout A549 cells. In line with the transcriptional assays, compounds 2 and 7 also significantly lowered CCL-2 chemokine production, albeit to a lesser extent than Dex. The results suggest that daucanes may be interesting candidates in the search for compounds with GR-modulating activities.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0163-3864
1520-6025
DOI:10.1021/acs.jnatprod.7b00012