Essential oils (EOs) of culinary herbs and spices are consumed on a daily basis. They are multicomponent mixtures of compounds with already demonstrated biological activities. Taking into account regular dietary intake and the chemical composition of EOs, they may be considered as candidates for endocrine-disrupting entities. Therefore, we examined the effects of 31 EOs of culinary herbs and spices on transcriptional activities of glucocorticoid receptor (GR), androgen receptor (AR) and vitamin D receptor (VDR). Using reporter gene assays in stably transfected cell lines, weak anti-androgen and anti-glucocorticoid activity was observed for EO of vanilla and nutmeg, respectively. Moderate augmentation of calcitriol-dependent VDR activity was caused by EOs of ginger, thyme, coriander and lemongrass. Mixed anti-glucocorticoid and VDR-stimulatory activities were displayed by EOs of turmeric, oregano, dill, caraway, verveine and spearmint. The remaining 19 EOs were inactive against all receptors under investigation. Analyses of GR, AR and VDR target genes by means of RT-PCR confirmed the VDR-stimulatory effects, but could not confirm the anti-glucocorticoid and anti-androgen effects of EOs. In conclusion, although we observed minor effects of several EOs on transcriptional activities of GR, AR and VDR, the toxicological significance of these effects is very low. Hence, 31 EOs of culinary herbs and spices may be considered safe, in terms of endocrine disruption involving receptors GR, AR and VDR.
- MeSH
- aktivace transkripce účinky léků MeSH
- androgenní receptory chemie metabolismus MeSH
- androgeny škodlivé účinky MeSH
- antagonisté androgenů škodlivé účinky MeSH
- endokrinní disruptory škodlivé účinky MeSH
- jedlé rostliny chemie MeSH
- koření * MeSH
- léčivé rostliny chemie MeSH
- lidé MeSH
- ligandy MeSH
- nádorové buněčné linie MeSH
- oleje prchavé škodlivé účinky MeSH
- receptory glukokortikoidů agonisté antagonisté a inhibitory genetika metabolismus MeSH
- receptory kalcitriolu agonisté antagonisté a inhibitory genetika metabolismus MeSH
- regulace genové exprese účinky léků MeSH
- rekombinantní proteiny chemie metabolismus MeSH
- reportérové geny účinky léků MeSH
- reprodukovatelnost výsledků MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
Paricalcitol (19-nor-1,25/OH(2)/D(2)), a second generation vitamin D receptor (VDR) activator, is a synthetic analogue of vitamin D3. In contrast to calcitriol, paricalcitol has a reduced effect on intestinal calcium resorption thus avoiding undesirable hypercalcemia. Information about immunomodulatory activity of paricalcitol is scarce. In this study we show that, in all investigated aspects, paricalcitol retains significant immunomodulatory activity, comparable to calcitriol. Both VDR agonists impaired differentiation of immature dendritic cells (DCs) from monocytes. The presence of VDR agonists during DC differentiation abolished their capacity to be activated and, despite potent Toll-like receptor mediated stimulation, VDR agonist-treated DCs remained in the immature state. In accordance with these findings, VDR-treated DCs produced no bioactive IL-12 and had a significantly decreased capacity to induce antigen-specific T cells while the capacity to induce functional Tregs remained unchanged when compared to control DCs. As DCs and T cells play an important role in the pathogenesis of atherosclerosis, in end-stage renal disease patients, paricalcitol should be a VDR agonist of choice for the reduction of the risk of atherosclerosis due to its immunomodulatory effect proven in this study and known limited hypercalcemic effect. The immunomodulatory potency of paricalcitol makes it a drug of interest in the therapy of chronic immune-mediated inflammatory diseases.
- MeSH
- aktivace lymfocytů účinky léků MeSH
- buněčná diferenciace imunologie účinky léků MeSH
- CD8-pozitivní T-lymfocyty imunologie účinky léků MeSH
- dendritické buňky imunologie účinky léků MeSH
- ergokalciferoly farmakologie MeSH
- imunologické faktory farmakologie MeSH
- interleukin-12 biosyntéza imunologie MeSH
- kalcitriol farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- monocyty imunologie účinky léků MeSH
- receptory kalcitriolu antagonisté a inhibitory MeSH
- regulační T-lymfocyty imunologie účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH