Universiteit Leiden

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Mahmoud Halima

PhD candidate

Name
M. Halima MSc
Telephone
+31 71 527 4975
E-mail
m.halima@biology.leidenuniv.nl

Glucocorticoids (GCs) are steroid hormones that modulate inflammation, growth, metabolism and endocrine systems via the glucocorticoid receptor (GR). GCs over long periods triggers severe side effects due to provoking undesired transactivation activities and inducing unrequired trans-repression activity. Therefore, there is an urgent need to find novel GCs acting as selective GR agonists, capable to induce the desired immunosuppressive effects without promoting undesired transcriptional activities. The aim of this project is to elucidate the mechanism of action of ginsenosides and evaluate their therapeutic potential as anti-inflammatory drugs.

More information about Mahmoud Halima

We have investigated the anti-inflammatory properties of ginsenosides Rb1, Rg1, PPD, and PPT using the zebrafish tail fin amputation model. Our results demonstrate that these ginsenosides and their metabolites have anti-inflammatory activity in this assay and that Gr activation mediates the anti-inflammatory effects of these compounds, similar to that of a classical GC, beclomethasone. Using a glucosidase inhibitor, we demonstrated that cleavage of the glucose groups in Rg1 and Rb1 is required to exert their anti-inflammatory effects. In addition, Rb1, Rg1, PPD, PPT, and beclomethasone induced different alterations in the transcription of various immune-related genes, demonstrating differences in the selectivity of these GCs. We showed that PPD and Rb1 do not affect whole-body glucose levels, in contrast to a strong increase observed with beclomethasone. Furthermore, Rg1 and also PPT reduce whole-body glucose levels, which may improve the metabolic system of diabetics. Using the tail fin amputation assay, we obtained evidence that Rb1 and Rg1 are more selective Gr agonists than PPD and PPT, and that all these compounds are more selective than beclomethasone. While zebrafish larvae normally regenerate the amputated tail fin within several days, this process is completely inhibited by beclomethasone. PPD and PPT inhibit tissue regeneration in 70% of amputated tails, but Rb1 and Rg1 do not inhibit the regeneration of amputated tails. Finally, we showed that PPD and PPT inhibit cortisol secretion like beclomethasone, while Rb1 and Rg1 do not affect the whole body cortisol level. Altogether, our data provide new evidence that Rb1 and Rg1 can be further developed as selective Gr agonists with effective anti-inflammatory action and reduced side effects. We hypothesize that the glucose moieties, which are present mainly on Rb1 and Rg1, make them more selective than PPT and PPD and classical GCS. Experiments to test this hypothesis are ongoing.

PhD candidate

  • Science
  • Instituut Biologie Leiden
  • IBL Animal Sciences

Work address

Sylvius
Sylviusweg 72
2333 BE Leiden

Contact

Publications

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