Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae
Glucocorticoids are effective anti-inflammatory drugs, but their clinical use is complicated due to the wide range of side effects they induce. Patients requiring glucocorticoid therapy would benefit from more selective glucocorticoid receptor (GR) agonists, capable of attenuating the immune respons...
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doaj-1b2de57e156b41939b21c3f9602a64822020-11-25T03:03:16ZengMDPI AGCells2073-44092020-04-0191107110710.3390/cells9051107Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish LarvaeMin He0Mahmoud Halima1Yufei Xie2Marcel J. M. Schaaf3Annemarie H. Meijer4Mei Wang5Institute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsInstitute of Biology Leiden, Leiden University, 2333CC Leiden, The NetherlandsGlucocorticoids are effective anti-inflammatory drugs, but their clinical use is complicated due to the wide range of side effects they induce. Patients requiring glucocorticoid therapy would benefit from more selective glucocorticoid receptor (GR) agonists, capable of attenuating the immune response without causing these side effects. Ginsenosides, such as the compound Rg1, are natural plant compounds with structural similarity to classical glucocorticoids and well-documented anti-inflammatory effects. Here, we have investigated the activity of the ginsenoside Rg1 using a zebrafish larval model, in which amputation of the tail fin allows us to assess drug effects on inflammation, while the ability to regenerate the wounded tissue serves as a readout for side effects. We found that Rg1 attenuates neutrophilic inflammation at the amputation site, similarly to a classical glucocorticoid, beclomethasone. Mutation of the Gr abolishes this anti-inflammatory effect of Rg1. Rg1 and beclomethasone differentially modulate gene expression, suggesting that Rg1 induces transrepression, but not transactivation, activity of Gr. Interestingly, we found no effect of Rg1 on tissue regeneration, whereas beclomethasone inhibits tissue regeneration entirely. We conclude that Rg1 is a promising candidate for development as a selective glucocorticoid drug, and that zebrafish larvae provide a useful model system for screening of such GR agonists.https://www.mdpi.com/2073-4409/9/5/1107ginsenosideRg1zebrafishtail fin amputationinflammationglucocorticoid |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Min He Mahmoud Halima Yufei Xie Marcel J. M. Schaaf Annemarie H. Meijer Mei Wang |
spellingShingle |
Min He Mahmoud Halima Yufei Xie Marcel J. M. Schaaf Annemarie H. Meijer Mei Wang Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae Cells ginsenoside Rg1 zebrafish tail fin amputation inflammation glucocorticoid |
author_facet |
Min He Mahmoud Halima Yufei Xie Marcel J. M. Schaaf Annemarie H. Meijer Mei Wang |
author_sort |
Min He |
title |
Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae |
title_short |
Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae |
title_full |
Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae |
title_fullStr |
Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae |
title_full_unstemmed |
Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae |
title_sort |
ginsenoside rg1 acts as a selective glucocorticoid receptor agonist with anti-inflammatory action without affecting tissue regeneration in zebrafish larvae |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2020-04-01 |
description |
Glucocorticoids are effective anti-inflammatory drugs, but their clinical use is complicated due to the wide range of side effects they induce. Patients requiring glucocorticoid therapy would benefit from more selective glucocorticoid receptor (GR) agonists, capable of attenuating the immune response without causing these side effects. Ginsenosides, such as the compound Rg1, are natural plant compounds with structural similarity to classical glucocorticoids and well-documented anti-inflammatory effects. Here, we have investigated the activity of the ginsenoside Rg1 using a zebrafish larval model, in which amputation of the tail fin allows us to assess drug effects on inflammation, while the ability to regenerate the wounded tissue serves as a readout for side effects. We found that Rg1 attenuates neutrophilic inflammation at the amputation site, similarly to a classical glucocorticoid, beclomethasone. Mutation of the Gr abolishes this anti-inflammatory effect of Rg1. Rg1 and beclomethasone differentially modulate gene expression, suggesting that Rg1 induces transrepression, but not transactivation, activity of Gr. Interestingly, we found no effect of Rg1 on tissue regeneration, whereas beclomethasone inhibits tissue regeneration entirely. We conclude that Rg1 is a promising candidate for development as a selective glucocorticoid drug, and that zebrafish larvae provide a useful model system for screening of such GR agonists. |
topic |
ginsenoside Rg1 zebrafish tail fin amputation inflammation glucocorticoid |
url |
https://www.mdpi.com/2073-4409/9/5/1107 |
work_keys_str_mv |
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