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. 2025 May 30:16:1601384.
doi: 10.3389/fphar.2025.1601384. eCollection 2025.

Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction

Xinqi Li #  1 , Guizhou Hu #  1   2 , Xu Chen  3 , Can Di  3 , Jin Qi  1
Affiliations

Screening and identification of the H1R antagonists from natural products by BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction

Xinqi Li et al. Front Pharmacol. .

Abstract

Introduction: Histamine 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.

Methods: In 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.

Results: The 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.

Conclusion: This 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.

Keywords: BODIPY FL histamine; H1R antagonists; HPLC-Q-TOF-MS; dictamnine; natural products; pseudoephedrine; target cell extraction.

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Conflict of interest statement

Author GH was employed by Jiangsu Kanion Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Rapid method of identifying the H1R antagonists using the BODIPY FL histamine recognition and DPHD-anchored bombardment coupled with target cell extraction.
FIGURE 2
FIGURE 2
Establishing and optimizing of the BODIPY FL histamine recognition of H1R antagonists. (A) DPHD; (B) loratadine; (C) incubation concentration of BODIPY FL histamine; (D) incubation time of BODIPY FL histamine; (E) washing times; (F) incubation time of diphenhydramine. (**p < 0.01 and ****p < 0.0001 compared to the control group).
FIGURE 3
FIGURE 3
Effect of different extracts on the viability of HUVECs and the BODIPY FL histamine. (A,C) ESS; (B,D) DdT (*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 compared to the control group).
FIGURE 4
FIGURE 4
MS chromatogram and structural formula of potential active components of the eluent of HUVECs binding with DdT [(A): a: DdT; b: DdT+DPHD)] and ESS [(B): a: ESS; b: ESS+DPHD)].
FIGURE 5
FIGURE 5
Effect of different potentially active components on the viability of HUVECs and the BODIPY FL histamine. (A,E) ephedrine; (B,F) pseudoephedrine; (C,G) dictamnine; (D,H) limonin. (*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 compared to the control group).
FIGURE 6
FIGURE 6
Inhibition effect of dictamnine on intracellular Ca2+ increase induced by histamine. Concentration of dictamnine: (A) 0; (B) 25 μM; (C) 50 μM; (D) 100 μM. (E) AUC statistic of the above groups (****p < 0.0001, compared with the histamine group-dictamnine 0 μM).
FIGURE 7
FIGURE 7
Inhibition effect of pseudoephedrine on intracellular Ca2+ increase induced by histamine. Concentration of pseudoephedrine: (A) 0; (B) 50 μM; (C) 100 μM; (D) 200 μM, (E) AUC statistic of the above groups (*p < 0.05, compared with the histamine group-pseudoephedrine 0 μM).
FIGURE 8
FIGURE 8
Three-dimensional and two-dimensional docking models of components with H1R generated by Discovery Studio Visualizer. (A,B) Pseudoephedrine; (C,D) dictamnine.
FIGURE 9
FIGURE 9
Effects of dictamnine on body weight, behavior, and serum cytokine levels of AR mice. (A) Initial weight; (B) final weight; (C) weight curve, (D) rubbing; (E) sneezing, (F) histamine (HIS); (G) IgE; (H) TNF-α; (I) IL-2; (J) IL-5; (K) IL-6 (###p < 0.001 compared to the control group; *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the model group).
FIGURE 10
FIGURE 10
Effect of dictamnine on histological changes in the nasal mucosa and lung of AR mice. (A) HE staining (nasal mucosa, 200x); (B) PAS staining (nasal mucosa, 200x); (C) HE (lung, 400x).
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References

    1. Abd Rani N. Z., Lam K. W., Jalil J., Mohamad H. F., Mat Ali M. S., Husain K. (2021). Mechanistic studies of the antiallergic activity of Phyllanthus amarus schum. and thonn. And its compounds. Molecules 26 (3), 695. 10.3390/molecules26030695 - DOI - PMC - PubMed
    1. Adderley S. P., Zhang X. E., Breslin J. W. (2015). Involvement of the H1 histamine receptor, p38 MAP kinase, myosin light chains kinase, and rho/ROCK in histamine-induced endothelial barrier dysfunction. Microcirculation 22 (4), 237–248. 10.1111/micc.12189 - DOI - PMC - PubMed
    1. Allikalt A., Laasfeld T., Ilisson M., Kopanchuk S., Rinken A. (2021). Quantitative analysis of fluorescent ligand binding to dopamine D(3) receptors using live-cell microscopy. Febs J. 288 (5), 1514–1532. 10.1111/febs.15519 - DOI - PubMed
    1. Arruda M. A., Stoddart L. A., Gherbi K., Briddon S. J., Kellam B., Hill S. J. (2017). A non-imaging high throughput approach to chemical library screening at the unmodified adenosine-A(3) receptor in living cells. Front. Pharmacol. 8, 908. 10.3389/fphar.2017.00908 - DOI - PMC - PubMed
    1. Bosma R., Moritani R., Leurs R., Vischer H. F. (2016). BRET-based β-arrestin2 recruitment to the histamine H1 receptor for investigating antihistamine binding kinetics. Pharmacol. Res. 111, 679–687. 10.1016/j.phrs.2016.07.034 - DOI - PubMed

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