Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model
Abstract Allergy is an immune-mediated disorder characterized by an exaggerated response of the immune system to non-hazardous substances, resulting in allergic symptoms such as rash, itching, and runny nose. Current therapeutic interventions include antihistamines and steroids; however, they induce...
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2025-01-01
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author | Sugeun Gwon Seong-Ah Shin Moonsu Kim Sun Young Moon Seyeon Choi Minji Kim Jun Hyuck Lee Hyun Ho Park Chang Sup Lee |
author_facet | Sugeun Gwon Seong-Ah Shin Moonsu Kim Sun Young Moon Seyeon Choi Minji Kim Jun Hyuck Lee Hyun Ho Park Chang Sup Lee |
author_sort | Sugeun Gwon |
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description | Abstract Allergy is an immune-mediated disorder characterized by an exaggerated response of the immune system to non-hazardous substances, resulting in allergic symptoms such as rash, itching, and runny nose. Current therapeutic interventions include antihistamines and steroids; however, they induce several side effects. Although 5,7-dihydroxy-4-methylcoumarin, a phytochemical derivative, has been demonstrated to exhibit antioxidant, anti-apoptotic, and anti-aggregatory effects, its anti-allergic properties and underlying molecular mechanisms remain elusive. Therefore, this study was conducted to investigate the anti-allergic effects of 5,7-dihydroxy-4-methylcoumarin in two experimental models: rat basophilic leukemia-2H3 cells sensitized using dinitrophenyl-specific immunoglobulin E (IgE)/human serum albumin and a passive cutaneous anaphylaxis (PCA) murine model. Our findings demonstrated that 5,7-dihydroxy-4-methylcoumarin reduced the release of histamine and β-hexosaminidase and downregulated the mRNA expression of allergic-inflammatory cytokines, such as interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha, as well as the inflammatory enzyme cyclooxygenase-2. Furthermore, 5,7-dihydroxy-4-methylcoumarin reduced the phosphorylation of mitogen-activated protein kinases such as extracellular signal-regulated kinase and p38, as well as protein kinase B. In vivo, 5,7-dihydroxy-4-methylcoumarin reduced PCA reaction, as evidenced by reduced Evans blue dye extravasation in IgE-mediated local allergic responses. Collectively, these results suggest that 5,7-dihydroxy-4-methylcoumarin holds promise as a novel candidate for the development of anti-allergic drugs. |
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language | English |
publishDate | 2025-01-01 |
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series | Applied Biological Chemistry |
spelling | doaj-art-df5f2dedddba4598a383096ba326bf222025-01-19T12:36:37ZengSpringerOpenApplied Biological Chemistry2468-08422025-01-0168111010.1186/s13765-025-00980-4Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine modelSugeun Gwon0Seong-Ah Shin1Moonsu Kim2Sun Young Moon3Seyeon Choi4Minji Kim5Jun Hyuck Lee6Hyun Ho Park7Chang Sup Lee8College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityResearch Unit of Cryogenic Novel Materials, Korea Polar Research InstituteCollege of Pharmacy, Chung-Ang UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National UniversityAbstract Allergy is an immune-mediated disorder characterized by an exaggerated response of the immune system to non-hazardous substances, resulting in allergic symptoms such as rash, itching, and runny nose. Current therapeutic interventions include antihistamines and steroids; however, they induce several side effects. Although 5,7-dihydroxy-4-methylcoumarin, a phytochemical derivative, has been demonstrated to exhibit antioxidant, anti-apoptotic, and anti-aggregatory effects, its anti-allergic properties and underlying molecular mechanisms remain elusive. Therefore, this study was conducted to investigate the anti-allergic effects of 5,7-dihydroxy-4-methylcoumarin in two experimental models: rat basophilic leukemia-2H3 cells sensitized using dinitrophenyl-specific immunoglobulin E (IgE)/human serum albumin and a passive cutaneous anaphylaxis (PCA) murine model. Our findings demonstrated that 5,7-dihydroxy-4-methylcoumarin reduced the release of histamine and β-hexosaminidase and downregulated the mRNA expression of allergic-inflammatory cytokines, such as interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha, as well as the inflammatory enzyme cyclooxygenase-2. Furthermore, 5,7-dihydroxy-4-methylcoumarin reduced the phosphorylation of mitogen-activated protein kinases such as extracellular signal-regulated kinase and p38, as well as protein kinase B. In vivo, 5,7-dihydroxy-4-methylcoumarin reduced PCA reaction, as evidenced by reduced Evans blue dye extravasation in IgE-mediated local allergic responses. Collectively, these results suggest that 5,7-dihydroxy-4-methylcoumarin holds promise as a novel candidate for the development of anti-allergic drugs.https://doi.org/10.1186/s13765-025-00980-45,7-Dihydroxy-4-methylcoumarinAnti-allergyRBL-2H3 cellPassive cutaneous anaphylaxis murine model |
spellingShingle | Sugeun Gwon Seong-Ah Shin Moonsu Kim Sun Young Moon Seyeon Choi Minji Kim Jun Hyuck Lee Hyun Ho Park Chang Sup Lee Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model Applied Biological Chemistry 5,7-Dihydroxy-4-methylcoumarin Anti-allergy RBL-2H3 cell Passive cutaneous anaphylaxis murine model |
title | Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model |
title_full | Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model |
title_fullStr | Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model |
title_full_unstemmed | Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model |
title_short | Anti-allergic effect of 5,7-dihydroxy-4-methylcoumarin in IgE-mediated RBL-2H3 cells and PCA murine model |
title_sort | anti allergic effect of 5 7 dihydroxy 4 methylcoumarin in ige mediated rbl 2h3 cells and pca murine model |
topic | 5,7-Dihydroxy-4-methylcoumarin Anti-allergy RBL-2H3 cell Passive cutaneous anaphylaxis murine model |
url | https://doi.org/10.1186/s13765-025-00980-4 |
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