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Involvement of the glucocorticoid receptor in pro-inflammatory transcription factor inhibition by daucane esters from Laserpitium zernyi

(2017) JOURNAL OF NATURAL PRODUCTS. 80(5). p.1505-1513
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Abstract
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) a 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-kappa B 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 2 beta-angeloyloxy-10 alpha-acetoxy-8-daucene-2,4,10-triol (2) significantly inhibited transactivation of both NF-kappa B 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-kappa B 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.
Keywords
FERULA-COMMUNIS, CAROTANE SESQUITERPENES, CYTOTOXIC ACTIVITY, GENE, REPRESSION, KAPPA-B, CONSTITUENTS, PROTEIN-1, ARRIGONII, LACTONES, LINKII

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Citation

Please use this url to cite or link to this publication:

Chicago
Popovic, Visnja, Jan Goeman, Nadia Bougarne, Sven Eyckerman, Arne Heyerick, Karolien De Bosscher, and Johan Van der Eycken. 2017. “Involvement of the Glucocorticoid Receptor in Pro-inflammatory Transcription Factor Inhibition by Daucane Esters from Laserpitium Zernyi.” Journal of Natural Products 80 (5): 1505–1513.
APA
Popovic, V., Goeman, J., Bougarne, N., Eyckerman, S., Heyerick, A., De Bosscher, K., & Van der Eycken, J. (2017). Involvement of the glucocorticoid receptor in pro-inflammatory transcription factor inhibition by daucane esters from Laserpitium zernyi. JOURNAL OF NATURAL PRODUCTS, 80(5), 1505–1513.
Vancouver
1.
Popovic V, Goeman J, Bougarne N, Eyckerman S, Heyerick A, De Bosscher K, et al. Involvement of the glucocorticoid receptor in pro-inflammatory transcription factor inhibition by daucane esters from Laserpitium zernyi. JOURNAL OF NATURAL PRODUCTS. 2017;80(5):1505–13.
MLA
Popovic, Visnja, Jan Goeman, Nadia Bougarne, et al. “Involvement of the Glucocorticoid Receptor in Pro-inflammatory Transcription Factor Inhibition by Daucane Esters from Laserpitium Zernyi.” JOURNAL OF NATURAL PRODUCTS 80.5 (2017): 1505–1513. Print.
@article{8534809,
  abstract     = {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) a 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-kappa B 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 2 beta-angeloyloxy-10 alpha-acetoxy-8-daucene-2,4,10-triol (2) significantly inhibited transactivation of both NF-kappa B 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-kappa B 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.},
  author       = {Popovic, Visnja and Goeman, Jan and Bougarne, Nadia and Eyckerman, Sven and Heyerick, Arne and De Bosscher, Karolien and Van der Eycken, Johan},
  issn         = {0163-3864},
  journal      = {JOURNAL OF NATURAL PRODUCTS},
  language     = {eng},
  number       = {5},
  pages        = {1505--1513},
  title        = {Involvement of the glucocorticoid receptor in pro-inflammatory transcription factor inhibition by daucane esters from Laserpitium zernyi},
  url          = {http://dx.doi.org/10.1021/acs.jnatprod.7b00012},
  volume       = {80},
  year         = {2017},
}

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