1- Faculty of Science and Modern Technologies, Semnan University, Semnan, Iran
2- Department of Cell and Molecular Biology, Faculty of Science, Semnan University ,mehdisadeghi@semnan.ac.ir
2- Department of Cell and Molecular Biology, Faculty of Science, Semnan University ,
Abstract: (324 Views)
Background: Histamine plays a crucial role in regulating diverse physiological and pathophysiological functions, including gastric acid secretion, vasodilation, and bronchoconstriction. As a neurotransmitter, it is also implicated in allergic reactions, contributing to symptoms such as itching, sneezing, and inflammation. Given the potential adverse effects of histamine activity, antihistamines are frequently prescribed to mitigate its effects. However, the associated side effects of these drugs have prompted researchers to investigate natural alternatives, such as curcumin from turmeric and catechins from green tea. This study investigates the potential effect of curcumin and catechin on the histamine N-methyltransferase (HNMT) receptor and its T105I and L208P mutant variants.
Methods: Molecular docking was employed to analyze ligand-receptor interactions. The protein structure was obtained from the Protein Data Bank (PDB), and ligands were retrieved from PubChem. Ligand structures were optimized using Avogadro software, and docking studies were subsequently performed using AutoDock Tools and the Vina algorithm.
Results: Molecular docking studies have demonstrated strong binding affinities of catechin and curcumin to the target protein, with binding energies of -8.5 and -8.4 kcal/mol, respectively, which is more than twice the binding affinity of histamine (-4.0 kcal/mol). Analysis of docking results with variant proteins revealed a slight reduction in ligand binding energies compared to the normal protein. These findings suggest that both catechin and curcumin hold promise as potential therapeutic agents for patients with the studied variants of the target protein. Furthermore, docking analysis revealed key stabilizing interactions, including π–π stacking and hydrogen bonding.
Conclusion: Phe243 is a key binding site residue in HNMT, showing consistent strong interactions with all tested ligands. Its structural flexibility enables effective binding to compounds like catechin and curcumin, making it a prime target for designing new HNMT inhibitors.
Methods: Molecular docking was employed to analyze ligand-receptor interactions. The protein structure was obtained from the Protein Data Bank (PDB), and ligands were retrieved from PubChem. Ligand structures were optimized using Avogadro software, and docking studies were subsequently performed using AutoDock Tools and the Vina algorithm.
Results: Molecular docking studies have demonstrated strong binding affinities of catechin and curcumin to the target protein, with binding energies of -8.5 and -8.4 kcal/mol, respectively, which is more than twice the binding affinity of histamine (-4.0 kcal/mol). Analysis of docking results with variant proteins revealed a slight reduction in ligand binding energies compared to the normal protein. These findings suggest that both catechin and curcumin hold promise as potential therapeutic agents for patients with the studied variants of the target protein. Furthermore, docking analysis revealed key stabilizing interactions, including π–π stacking and hydrogen bonding.
Conclusion: Phe243 is a key binding site residue in HNMT, showing consistent strong interactions with all tested ligands. Its structural flexibility enables effective binding to compounds like catechin and curcumin, making it a prime target for designing new HNMT inhibitors.
Keywords: Curcumin, Catechin, Histamine N-Methyltransferase, Molecular Docking (Molecular Docking Simulation)
Type of Article: Original article |
Subject:
Molecular Sciences
Received: 2025/05/26 | Accepted: 2025/10/1
Received: 2025/05/26 | Accepted: 2025/10/1
References
1. Akdis CA, Simons FER. Histamine receptors are hot in immunopharmacology. Eur J Pharmacol. 2006;533(1-3):69-76. [View at Publisher] [DOI] [PMID] [Google Scholar]
2. Thangam EB, Jemima EA, Singh H, Baig MS, Khan M, Mathias CB, et al. The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets. Front Immunol. 2018;9:1873. [View at Publisher] [DOI] [PMID] [Google Scholar]
3. Hrubisko M, Danis R, Huorka M, Wawruch M. Histamine Intolerance-The More We Know the Less We Know. A Review. Nutrients. 2021;13(7):2228. [View at Publisher] [DOI] [PMID] [Google Scholar]
4. Joskova M, Mokry J, Franova S. Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors. Front Pharmacol. 2020;11:609. [View at Publisher] [DOI] [PMID] [Google Scholar]
5. Li J, Sun C, Cai W, Li J, Rosen BP, Chen J. Insights into S-adenosyl-l-methionine (SAM)-dependent methyltransferase related diseases and genetic polymorphisms. Mutat Res Rev Mutat Res. 2021;788:108396. [View at Publisher] [DOI] [PMID] [Google Scholar]
6. Horton JR, Sawada K, Nishibori M, Zhang X, Cheng X. Two Polymorphic Forms of Human Histamine Methyltransferase. Structure. 2001;9(9):837- 49. [View at Publisher] [DOI] [PMID] [Google Scholar]
7. Lee HS, Kim S-H, Kim KW, Baek JY, Park H-S, Lee KE, et al. Involvement of human histamine N-methyltransferase gene polymorphisms in susceptibility to atopic dermatitis in Korean children. Allergy Asthma Immunol Res. 2012;4(1):31-6. [View at Publisher] [DOI] [PMID] [Google Scholar]
8. Gielecińska A, Kciuk M, Mujwar S, Celik I, Kołat D, Kałuzińska-Kołat Ż, et al. Substances of Natural Origin in Medicine: Plants vs. Cancer. Cells. 2023;12(7):986. [View at Publisher] [DOI] [PMID] [Google Scholar]
9. Hewlings SJ, Kalman DS. Curcumin: A Review of Its Effects on Human Health. Foods. 2017;6(10):92. [View at Publisher] [DOI] [PMID] [Google Scholar]
10. Isemura M. Catechin in Human Health and Disease. Molecules. 2019;24(3):528. [View at Publisher] [DOI] [PMID] [Google Scholar]
11. Morris GM, Lim-Wilby M. Molecular Docking. Methods Mol Biol. 2008:443:365-82. [View at Publisher] [DOI] [PMID] [Google Scholar]
12. Jiménez EM, Żołek T, Hernández Perez PG, Miranda Ruvalcaba R, Nicolás-Vázquez MI, Hernández-Rodríguez M. Drug Repurposing to Inhibit Histamine N-Methyl Transferase. Molecules. 2023;28(2):576. [View at Publisher] [DOI] [PMID] [Google Scholar]
13. Mikou A, Cabayé A, Goupil A, Bertrand H-O, Mothet J-P, Acher FC. Asc-1 Transporter (SLC7A10): Homology Models And Molecular Dynamics Insights Into The First Steps Of The Transport Mechanism. Sci Rep. 2020;10(1):3731. [View at Publisher] [DOI] [PMID] [Google Scholar]
14. Farag NA, Mohamed SR, Soliman GAH. Design, synthesis, and docking studies of novel benzopyrone derivatives as H1-antihistaminic agents. Bioorg Med Chem. 2008;16(19):9009-17. [View at Publisher] [DOI] [PMID] [Google Scholar]
15. Chu Q, Sun S, Li C, Qu G, Sun Z. Elucidating the impact of S-adenosylmethionine and histamine binding on N-methyltransferase conformational dynamics: Insights from an in silico study. J Mol Graph Model. 2025;136:108961. [View at Publisher] [DOI] [PMID] [Google Scholar]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
