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<p>The role of histamine H3 receptor (H3R) in the pathogenesis of neurodegenerative diseases is well known. The development of non-imidazole-based drugs against it is being actively pursued, and full effectiveness has not yet been attained. To address this issue and to identify other potential candidates with better therapeutic values, computational modelling was performed with the phytochemicals of an ethnobotanically significant plant, <i>Panax ginseng</i> C.A. Meyer, against H3R. The flexible receptor molecular docking calculations revealed baicalin (− 10.850), ergosterol (− 10.740), and dammarene (− 10.533) as the top scorers (binding affinity, kcal/mol) against the target protein with PDB ID of 7F61. The interaction was better than that observed for the native ligand (− 10.647) and eleven drugs (minimum of − 10.689) but was weaker than that for the drug, ABT-239 (− 11.087). The spatial stability of the top adducts was indicated by the smooth curves of ligand root mean square deviation (RMSD) and by its variation below 2 Å from molecular dynamics simulations (MDS) of 200 ns duration. The binding free energy changes (kcal/mol) for baicalin (− 39.37 ± 5.34) and dammarene (− 31.56 ± 4.27) containing adducts hinted at pronounced thermodynamical stability and sustained spontaneity of the complex formation reaction. Various structural descriptors (pair distribution function, hydrogen bond modulation, and distribution) inferred to localized nature of the docked poses. The formation of stable adducts showed the possibility of the inhibition of the receptor leading to the management of neurodegenerative disorders. The top candidates could be suggested for further in vitro and in vivo experiments to validate the preliminary modelling results.</p>

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Phytochemicals of Panax ginseng C.A. Meyer against Histamine H3 receptor by computational modelling

  • 期刊论文

  • 发表日期：

    2025年6月23日

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  • Ram Lal Swagat Shrestha,
  • Jhashanath Adhikari Subin

摘要

The role of histamine H3 receptor (H3R) in the pathogenesis of neurodegenerative diseases is well known. The development of non-imidazole-based drugs against it is being actively pursued, and full effectiveness has not yet been attained. To address this issue and to identify other potential candidates with better therapeutic values, computational modelling was performed with the phytochemicals of an ethnobotanically significant plant, Panax ginseng C.A. Meyer, against H3R. The flexible receptor molecular docking calculations revealed baicalin (− 10.850), ergosterol (− 10.740), and dammarene (− 10.533) as the top scorers (binding affinity, kcal/mol) against the target protein with PDB ID of 7F61. The interaction was better than that observed for the native ligand (− 10.647) and eleven drugs (minimum of − 10.689) but was weaker than that for the drug, ABT-239 (− 11.087). The spatial stability of the top adducts was indicated by the smooth curves of ligand root mean square deviation (RMSD) and by its variation below 2 Å from molecular dynamics simulations (MDS) of 200 ns duration. The binding free energy changes (kcal/mol) for baicalin (− 39.37 ± 5.34) and dammarene (− 31.56 ± 4.27) containing adducts hinted at pronounced thermodynamical stability and sustained spontaneity of the complex formation reaction. Various structural descriptors (pair distribution function, hydrogen bond modulation, and distribution) inferred to localized nature of the docked poses. The formation of stable adducts showed the possibility of the inhibition of the receptor leading to the management of neurodegenerative disorders. The top candidates could be suggested for further in vitro and in vivo experiments to validate the preliminary modelling results.