Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)
Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been r...
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doaj-dce5215f00404c6d90f86b04e10d50562020-11-25T01:15:29ZengMDPI AGMolecules1420-30492020-02-01255102810.3390/molecules25051028molecules25051028Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)Mukesh Kumar0Kailash Singh1Karthi Duraisamy2Ahmed A. Allam3Jamaan Ajarem4Billy Kwok Chong CHOW5School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, ChinaSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, ChinaSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, ChinaDepartment of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, EgyptDepartment of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaSchool of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, ChinaAnaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2.https://www.mdpi.com/1420-3049/25/5/1028anaphylactoid shockmast cellsallergymrgprx2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mukesh Kumar Kailash Singh Karthi Duraisamy Ahmed A. Allam Jamaan Ajarem Billy Kwok Chong CHOW |
spellingShingle |
Mukesh Kumar Kailash Singh Karthi Duraisamy Ahmed A. Allam Jamaan Ajarem Billy Kwok Chong CHOW Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) Molecules anaphylactoid shock mast cells allergy mrgprx2 |
author_facet |
Mukesh Kumar Kailash Singh Karthi Duraisamy Ahmed A. Allam Jamaan Ajarem Billy Kwok Chong CHOW |
author_sort |
Mukesh Kumar |
title |
Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) |
title_short |
Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) |
title_full |
Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) |
title_fullStr |
Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) |
title_full_unstemmed |
Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2) |
title_sort |
protective effect of genistein against compound 48/80 induced anaphylactoid shock via inhibiting mas related g protein-coupled receptor x2 (mrgprx2) |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2020-02-01 |
description |
Anaphylactoid shock is a fatal hypersensitivity response caused by non-IgE mediated mast cell activation. These reactions are mediated by a family of G protein-coupled receptors (GPCRs) known as Mas related GPCRX2 (MRGPRX2). Several US FDA approved drugs which are used in day to day life have been reported to cause anaphylactoid shock. Surprisingly, no therapeutic drugs are available which can directly target MRGPRX2 for treatment of anaphylactoid shock. Genistein is a non-steroidal polyphenol known for its diverse physiological and pharmacological activities. In recent studies, Genistein has been reported for its anti-inflammatory activity on mast cells. However, the effects and mechanistic pathways of Genistein on anaphylactoid reaction remain unknown. In the present study, we designed a battery of in-vitro, in-silico and in-vivo experiments to evaluate the anti-anaphylactoid activity of Genistein in order to understand the possible molecular mechanisms of its action. The in-vitro results demonstrated the inhibitory activity of Genistein on MRGPRX2 activation. Further, a mouse model of anaphylactoid shock was used to evaluate the inhibitory activity of Genistein on blood vessel leakage and hind paw edema. Taken together, our findings have demonstrated a therapeutic potential of Genistein as a lead compound in the treatment of anaphylactoid shock via MRGPRX2. |
topic |
anaphylactoid shock mast cells allergy mrgprx2 |
url |
https://www.mdpi.com/1420-3049/25/5/1028 |
work_keys_str_mv |
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