Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae

He, Min; Halima, Mahmoud; Xie, Yujia; Schaaf, Marcel J. M.; Meijer, Annemarie H.; Wang, Mei

doi:10.3390/cells9051107

Cited by 28 publications

(30 citation statements)

References 50 publications

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“…In a previous study, we demonstrated the conserved role of tlr2 in zebrafish as a PRR to recognize the mammalian TLR2 ligand Pam3CSK4, and identified a set of genes that are specifically expressed by activation of the downstream pathway of zebrafish tlr2 ( Yang et al, 2015 ). Moreover, He et al (2020) confirmed that tlr2 gene expression can be upregulated upon wounding in zebrafish larvae which is consistent with previous studies in mice. In addition, the study of Sommer et al (2020a) suggests that myd88 is required for induction of chemokine gene expression, such as ccl2 and cxcl11aa , following tail wounding.…”

Section: Introductionsupporting

confidence: 92%

A Novel Function of TLR2 and MyD88 in the Regulation of Leukocyte Cell Migration Behavior During Wounding in Zebrafish Larvae

Steijn

et al. 2021

Front. Cell Dev. Biol.

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Toll-like receptor (TLR) signaling via myeloid differentiation factor 88 protein (MyD88) has been indicated to be involved in the response to wounding. It remains unknown whether the putative role of MyD88 in wounding responses is due to a control of leukocyte cell migration. The aim of this study was to explore in vivo whether TLR2 and MyD88 are involved in modulating neutrophil and macrophage cell migration behavior upon zebrafish larval tail wounding. Live cell imaging of tail-wounded larvae was performed in tlr2 and myd88 mutants and their corresponding wild type siblings. In order to visualize cell migration following tissue damage, we constructed double transgenic lines with fluorescent markers for macrophages and neutrophils in all mutant and sibling zebrafish lines. Three days post fertilization (dpf), tail-wounded larvae were studied using confocal laser scanning microscopy (CLSM) to quantify the number of recruited cells at the wounding area. We found that in both tlr2–/– and myd88–/– groups the recruited neutrophil and macrophage numbers are decreased compared to their wild type sibling controls. Through analyses of neutrophil and macrophage migration patterns, we demonstrated that both tlr2 and myd88 control the migration direction of distant neutrophils upon wounding. Furthermore, in both the tlr2 and the myd88 mutants, macrophages migrated more slowly toward the wound edge. Taken together, our findings show that tlr2 and myd88 are involved in responses to tail wounding by regulating the behavior and speed of leukocyte migration in vivo.

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Section: Introductionsupporting

confidence: 92%

A Novel Function of TLR2 and MyD88 in the Regulation of Leukocyte Cell Migration Behavior During Wounding in Zebrafish Larvae

Steijn

et al. 2021

Front. Cell Dev. Biol.

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“…Interestingly, the ginsenoside Rg1 was shown to inhibit neutrophil migration in a Gr-dependent manner, but did not show any effect on tissue regeneration. These data suggest that this compound may be provide an interesting lead for the development of novel anti-inflammatory drugs with reduced side effects (He et al, 2020 ).…”

Section: The Use Of Zebrafish Inflammation Models For Research On Glumentioning

confidence: 97%

“…Various natural products have been demonstrated to have an inhibitory effect on the infiltration of leukocytes near the wounded area, including extracts from the medicinal herb ginseng (roots of plants in the genus Panax, such as Panax ginseng ) (Sun et al, 2019 ). One of the bioactive compounds in these extracts was shown to be the ginsenoside Rg1, a glycosylated steroid that exerts its anti-inflammatory activity through the glucocorticoid receptor (GR) (He et al, 2020 ). Using a library of fungal extracts, two compounds, sterigmatocystin and the antibiotic PF1052, were found to inhibit neutrophil recruitment (Wang et al, 2014 ).…”

Section: Inflammatory Disease Models In Zebrafishmentioning

confidence: 99%

Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Xie

Meijer

Schaaf

2021

Front. Cell Dev. Biol.

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Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses in vivo at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (hai1a) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (cdipt) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.

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“…A recent study proved the anti-inflammatory effect without tissue regeneration of Ginsenoside Rg1 on the zebrafish model [78]. These results are related to the selective GR agonist action of Ginsenoside Rg1 [78].…”

Section: Ginsenoside Rg1mentioning

confidence: 91%

“…Ginsenoside Rg1 demonstrated a better therapeutic index in inhibition of acute and chronic inflammation without causing hyperglycemia or osteoporosis as seen with dexamethasone [77]. A recent study proved the anti-inflammatory effect without tissue regeneration of Ginsenoside Rg1 on the zebrafish model [78]. These results are related to the selective GR agonist action of Ginsenoside Rg1 [78].…”

Section: Ginsenoside Rg1mentioning

confidence: 95%

Selective Glucocorticoid Receptor Modulator: A Novel Class of Anti-inflammatory Compounds

Alsulaimani

2020

JPRI

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Background: Glucocorticoids exert a wide range of physiological effects. They effectively control various inflammatory and autoimmune diseases and play an important role in organ transplantation. Glucocorticoids are associated with unfavorable side effects that restrict their utilization. The most undesirable side effects are related to the transactivation of target genes. On the other hand, the transrepression of the genes is also responsible for the anti-inflammatory and immunomodulator of glucocorticoids. Principal Findings: The separation between these two processes through alteration in glucocorticoid receptor resulting in a compound with similar GCs benefit activity with fewer side effects. This review will discuss the molecular mechanism and summarizes the most common compounds and their beneficial effect in preclinical experiments. Conclusion: Several compounds that possess this feature are tested in preclinical experiments with promising results. These compounds are expected to be a better alternative to GCs drugs in the management of different diseases with a high degree of effectiveness.

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Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae

Cited by 28 publications

References 50 publications

A Novel Function of TLR2 and MyD88 in the Regulation of Leukocyte Cell Migration Behavior During Wounding in Zebrafish Larvae

A Novel Function of TLR2 and MyD88 in the Regulation of Leukocyte Cell Migration Behavior During Wounding in Zebrafish Larvae

Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs

Selective Glucocorticoid Receptor Modulator: A Novel Class of Anti-inflammatory Compounds

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