Identification of 20(R, S)-protopanaxadiol and 20(R, S)-protopanaxatriol for potential selective modulation of glucocorticoid receptor.
Food Chem Toxicol
; 131: 110642, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-31247261
ABSTRACT
Although glucocorticoids (GCs) are widely used as anti-inflammatory drugs, they are often accompanied by adverse effects, which are mainly due to the transactivation of glucocorticoid receptor (GR) target genes. In order to screen novel plant-derived GR ligands (phytocorticoids) capable of separating transrepression from transactivation, this work focuses on the estimation of 20(R, S)-protopanaxadiol [PPD(R, S)] and 20(R, S)-protopanaxatriol [PPT(R, S)] for their dissociated characteristics. The reporter gene assay shows that ginsenosides cannot enhance glucocorticoid-responsive element-driven genes. The cytotoxicity assay shows that PPT(S), PPT(R), and PPD(S) can inhibit cell proliferation while PPD(R) does not suppress cell growth at available concentration. Further analysis of transactivation and transrepression activities indicates that PPD(R) can repress the transcription of GR target transrepressed gene without activating the expression of the GR target transactivated gene. Results of molecular docking suggest that PPD(R) yields more hydrogen bond interactions and a lower binding energy than its counterparts, resulting in tighter binding between PPD(R) and GR. In addition, PPD(R) achieves stability in the pocket after 2â¯ns, thereby facilitating exerting its regulatory role of GR target genes. By contrast, other ginsenosides fluctuate drastically during the simulations. In conclusion, PPD(R) may serve as a potential selective GR modulator (SEGRM).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Sapogeninas
/
Receptores de Glucocorticoides
/
Ginsenosídeos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China