Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction
IntroductionHistamine is an important mediator of allergy, and inhibiting its binding to H1 receptors (H1R) is a key method to alleviate allergic diseases. Natural products with anti-allergic properties are an important source of natural H1R antagonists.MethodsIn this study, a rapid method for ident...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1601384/full |
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| author | Xinqi Li Guizhou Hu Guizhou Hu Xu Chen Can Di Jin Qi |
| author_facet | Xinqi Li Guizhou Hu Guizhou Hu Xu Chen Can Di Jin Qi |
| author_sort | Xinqi Li |
| collection | DOAJ |
| description | IntroductionHistamine is an important mediator of allergy, and inhibiting its binding to H1 receptors (H1R) is a key method to alleviate allergic diseases. Natural products with anti-allergic properties are an important source of natural H1R antagonists.MethodsIn this study, a rapid method for identifying the H1R antagonists from natural products via the BODIPY FL histamine recognition and diphenhydramine (DPHD)-anchored bombardment coupled with target cell extraction was developed. In addition, the activity of the H1R antagonist was further validated both in vitro and in vivo through BODIPY FL histamine recognition, intracellular fluorescence calcium ion (Ca2+) kinetic recognition, molecular docking, and animal experiments.ResultsThe binding of fluorescent histamine to H1R was notably inhibited by Ephedra sinica Stapf (ESS) and Dictamnus dasycarpus Turcz (DdT). Ephedrine and pseudoephedrine in ESS and dictamnine and limonin in DdT were screened as potential H1R antagonists using the target cell extraction of the DPHD-anchored bombardment. The BODIPY FL histamine recognition results revealed the significant blocking effects on H1R binding by pseudoephedrine (50 μM) and dictamnine (100 μM). Pseudoephedrine (200 μM) and dictamnine (100 μM) markedly decreased the histamine-induced increase in intracellular calcium ion (Ca2+) concentration. Docking results indicated strong binding affinity for both components to H1R, with dictamnine exhibiting a higher affinity than pseudoephedrine. Ultimately, the ameliorative effect of dictamnine on allergic rhinitis mice was confirmed through nasal symptom score, serum pharmacodynamic indices (immunoglobulin E (IgE), histamine, IL-2, IL-4, IL-6, and TNF-α), and histopathology.ConclusionThis study showed that dictamnine (validated in vitro and in vivo) and pseudoephedrine (validated in vitro) may serve as potential H1R antagonists. This study offered valuable insights for future developments in antihistamines. |
| format | Article |
| id | doaj-art-9c28ae0135cb48bc9035b127869dfea3 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-9c28ae0135cb48bc9035b127869dfea32025-08-20T02:01:29ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.16013841601384Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extractionXinqi Li0Guizhou Hu1Guizhou Hu2Xu Chen3Can Di4Jin Qi5Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaResearch Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaState Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, ChinaBYHEALTH Institute of Nutrition and Health, Guangzhou, ChinaBYHEALTH Institute of Nutrition and Health, Guangzhou, ChinaResearch Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntroductionHistamine is an important mediator of allergy, and inhibiting its binding to H1 receptors (H1R) is a key method to alleviate allergic diseases. Natural products with anti-allergic properties are an important source of natural H1R antagonists.MethodsIn this study, a rapid method for identifying the H1R antagonists from natural products via the BODIPY FL histamine recognition and diphenhydramine (DPHD)-anchored bombardment coupled with target cell extraction was developed. In addition, the activity of the H1R antagonist was further validated both in vitro and in vivo through BODIPY FL histamine recognition, intracellular fluorescence calcium ion (Ca2+) kinetic recognition, molecular docking, and animal experiments.ResultsThe binding of fluorescent histamine to H1R was notably inhibited by Ephedra sinica Stapf (ESS) and Dictamnus dasycarpus Turcz (DdT). Ephedrine and pseudoephedrine in ESS and dictamnine and limonin in DdT were screened as potential H1R antagonists using the target cell extraction of the DPHD-anchored bombardment. The BODIPY FL histamine recognition results revealed the significant blocking effects on H1R binding by pseudoephedrine (50 μM) and dictamnine (100 μM). Pseudoephedrine (200 μM) and dictamnine (100 μM) markedly decreased the histamine-induced increase in intracellular calcium ion (Ca2+) concentration. Docking results indicated strong binding affinity for both components to H1R, with dictamnine exhibiting a higher affinity than pseudoephedrine. Ultimately, the ameliorative effect of dictamnine on allergic rhinitis mice was confirmed through nasal symptom score, serum pharmacodynamic indices (immunoglobulin E (IgE), histamine, IL-2, IL-4, IL-6, and TNF-α), and histopathology.ConclusionThis study showed that dictamnine (validated in vitro and in vivo) and pseudoephedrine (validated in vitro) may serve as potential H1R antagonists. This study offered valuable insights for future developments in antihistamines.https://www.frontiersin.org/articles/10.3389/fphar.2025.1601384/fullBODIPY FL histamineH1R antagoniststarget cell extractionHPLC-Q-TOF-MSnatural productsdictamnine |
| spellingShingle | Xinqi Li Guizhou Hu Guizhou Hu Xu Chen Can Di Jin Qi Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction Frontiers in Pharmacology BODIPY FL histamine H1R antagonists target cell extraction HPLC-Q-TOF-MS natural products dictamnine |
| title | Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction |
| title_full | Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction |
| title_fullStr | Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction |
| title_full_unstemmed | Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction |
| title_short | Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction |
| title_sort | screening and identification of the h1r antagonists from natural products by bodipy fl histamine recognition and dphd anchored bombardment coupled with target cell extraction |
| topic | BODIPY FL histamine H1R antagonists target cell extraction HPLC-Q-TOF-MS natural products dictamnine |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1601384/full |
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