The structural diversity of ginsenosides affects their cholinesterase inhibitory potential

  • 1 Department of Biochemistry, Baskent Universitesi, Ankara, Turkey
  • 2 Hacettepe Universitesi, Ankara, Turkey
  • 3 Baskent Universitesi, Ankara, Turkey
Eda Özturan ÖzerORCID iD: https://orcid.org/0000-0001-6543-4043, Oya Unsal Tan and Suna Turkoglu

Abstract

Background/Objective

Ginsenosides, the major active components of the ginseng, are known to have various effects on nervous systems. The present study aimed to clarify the inhibition potentials of ginsenosides Rb1, Rc, Re and Rg1 on acetylcholinesterase (AChE) and butrylcholinesterase (BChE) activities, and to evaluate the underlying mechanisms of inhibitions provided by protein-ligand interactions considering their probable candidates of prodrug.

Materials and methods

The inhibitory mechanisms of ginsenosides related with their structural diversity were analyzed kinetically and protein-ligand interactions for both enzymes were evaluated with most potent ginsenosides, by molecular docking studies.

Results

Ginsenosides Re and Rg1, with sugar moieties attached to the C-6 and C-20 positions of core structure were found to possess the most powerful inhibitory effect on AChE and BChE activities. Molecular docking studies have been confirmed by kinetic studies. Ginsenosides having a direct interaction with amino acid residues belonging to the catalytic triad revealed the most powerful inhibition with lowest enzyme-inhibitor dissociation constant (Ki) values.

Conclusions

Ginsenosides Re and Rg1, either alone or in a specific combination, may provide beneficial effects on neurodegenerative pathologies in therapeutic terms.

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