Next Article in Journal
Iron Metabolism in Cancer
Next Article in Special Issue
Clinical Use and Molecular Action of Corticosteroids in the Pediatric Age
Previous Article in Journal
Identification and Functional Characterization of a Cold-Related Protein, BcHHP5, in Pak-Choi (Brassica rapa ssp. chinensis)
Previous Article in Special Issue
How Glucocorticoids Affect the Neutrophil Life
Open AccessArticle

Potential Dissociative Glucocorticoid Receptor Activity for Protopanaxadiol and Protopanaxatriol

1
Department of Biochemistry and Biotechnology, University of Thessaly, 41500 Larissa, Greece
2
School of Pharmacy & Biomedical Sciences, University of Central Lancashire, Preston PR12HE, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 94; https://doi.org/10.3390/ijms20010094
Received: 23 October 2018 / Revised: 21 December 2018 / Accepted: 21 December 2018 / Published: 27 December 2018
Glucocorticoids are steroid hormones that regulate inflammation, growth, metabolism, and apoptosis via their cognate receptor, the glucocorticoid receptor (GR). GR, acting mainly as a transcription factor, activates or represses the expression of a large number of target genes, among them, many genes of anti-inflammatory and pro-inflammatory molecules, respectively. Transrepression activity of glucocorticoids also accounts for their anti-inflammatory activity, rendering them the most widely prescribed drug in medicine. However, chronic and high-dose use of glucocorticoids is accompanied with many undesirable side effects, attributed predominantly to GR transactivation activity. Thus, there is a high need for selective GR agonist, capable of dissociating transrepression from transactivation activity. Protopanaxadiol and protopanaxatriol are triterpenoids that share structural and functional similarities with glucocorticoids. The molecular mechanism of their actions is unclear. In this study applying induced-fit docking analysis, luciferase assay, immunofluorescence, and Western blot analysis, we showed that protopanaxadiol and more effectively protopanaxatriol are capable of binding to GR to activate its nuclear translocation, and to suppress the nuclear factor-kappa beta activity in GR-positive HeLa and HEK293 cells, but not in GR-low level COS-7 cells. Interestingly, no transactivation activity was observed, whereas suppression of the dexamethasone-induced transactivation of GR and induction of apoptosis in HeLa and HepG2 cells were observed. Thus, our results indicate that protopanaxadiol and protopanaxatriol could be considered as potent and selective GR agonist. View Full-Text
Keywords: protopanaxadiol; protopanaxatriol; glucocorticoid receptor; SEGRA; apoptosis; inflammation; ginsenosides; tranactivation; tranrepression protopanaxadiol; protopanaxatriol; glucocorticoid receptor; SEGRA; apoptosis; inflammation; ginsenosides; tranactivation; tranrepression
Show Figures

Graphical abstract

MDPI and ACS Style

Karra, A.G.; Konstantinou, M.; Tzortziou, M.; Tsialtas, I.; Kalousi, F.D.; Garagounis, C.; Hayes, J.M.; Psarra, A.-M.G. Potential Dissociative Glucocorticoid Receptor Activity for Protopanaxadiol and Protopanaxatriol. Int. J. Mol. Sci. 2019, 20, 94.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop