Abstract
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.
Highlights
Acetylcholinesterase (AChE; E.C.3.1.1.7) and butyrylcholinestrase (BChE; E.C.3.1.1.8) are structurally and functionally related serine hydrolases present in various tissues including central nervous system
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
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
Summary
Acetylcholinesterase (AChE; E.C.3.1.1.7) and butyrylcholinestrase (BChE; E.C.3.1.1.8) are structurally and functionally related serine hydrolases present in various tissues including central nervous system. Their primary function is directly related with the cholinergic neurotransmission. Attenuation of cholinergic neurotransmission is achieved by the catalytic activities of cholinesterases, hydrolysis of esters of choline, mainly acetylcholine. Besides their regulator/co-regulator effect(s) on cholinergic neurotransmission, they probably contribute to the development of the nervous system and overall brain functions [1,2,3,4]. Potential therapeutic uses of human BChE for protection from nerve agent toxicity and for cocaine intoxication and cocaine addiction have been reported recently [2, 3, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
